Fucosylation inhibitors for preserving the viability of limbal stem cells

Abstract

The present disclosure relates to inhibitors of fucosylation, and pharmaceutical formulations thereof, for use in methods of preserving the viability of limbal stem cells, for use in methods of treating, inhibiting, or preventing limbal stem cell deficiency, and for use in methods for the treatment of ocular diseases.

Description

[0001]Attorney Docket No.: 00398-0184WO1 FUCOSYLATION INHIBITORS FOR PRESERVING THE VIABILITY OF LIMBAL STEM CELLS FIELD The present disclosure relates to inhibitors of fucosylation, and pharmaceutical formulations thereof, for preserving the viability of limbal stem cells, preventing limbal stem cell deficiency, and the treatment of ocular diseases. BACKGROUND Adult stem cells, also known as somatic or nonembryonic stem cells, are undifferentiated cells located within specialized niches in the adult organism. They are responsible for maintaining normal tissue turnover and mounting a regenerative response following acute injury. See, de Morree et al., Nat Rev Mol Cell Biol, 2023, 24, 334-354. These cells are characterized by a high capacity of self-renewal, slow cell cycle and ability to produce daughter cells that undergo differentiation. Populations of adult stem cells have been identified within multiple tissue types. In the corneal epithelium, stem cells localize to the basal layer at the transition zone between the peripheral cornea and the anterior sclera, in an area known as the limbus. From this location, limbal epithelial stem cells give rise to transient amplifying cells that migrate centripetally and anteriorly to generate the mature corneal epithelium. The limbal epithelial stem cell niche contains a distinctive basement membrane and is enriched with various cell populations, such as melanocytes and immune cells. Multiple lines of evidence indicate that this unique microenvironment is critical to the prevention of stem cell differentiation and defining stem cell fate. See, Secker et al., In StemBook, 2008, 10.3824 / stembook.1.48.1. The health of the cornea hinges upon continuous renewal of its epithelium by limbal stem cells (“LSCs”). In this manner, LSCs are indispensable for ocular health and their importance is illustrated in the condition of limbal stem cell deficiency (LSCD), which is characterized by the dysfunction or loss of LSCs. The absence of LSC manifests as persistent epithelial defects, corneal conjunctivalization, corneal opacity and ultimately visual impairment. LSCD is a leading cause of corneal blindness worldwide and can arise from many etiologies, ranging from traumatic to congenital. See, Barut Selver Ö et al., Turk J Ophthalmol, 2017, 47, 285-291. However, in all cases, irrespective of etiology, a key feature in the development of LSCD is ocular surface inflammation. In this context it is therefore of Attorney Docket No.: 00398-0184WO1 paramount importance to understand factors that regulate LSC survival in the face of inflammation. A number of glycans and / or glycan binding proteins are known to regulate inflammatory responses. See, Milusev et al., Sci Rep, 2023, 13, 4483. Carbohydrates found on glycoproteins and glycolipids in the glycocalyx play key roles in regulating the cell’s responsiveness to inflammatory mediators, via modulating intracellular signaling pathways and / or the interactions of cells with the microenvironment. See, Furukawa et al., J Biochem, 2012, 151, 573-578. The formation of the glycocalyx involves the coordinated action of nucleotide sugar transporters, hydrolases, and multiple glycosyltransferases that work together in the endoplasmic reticulum and Golgi apparatus to synthesize and modify glycan chains. See, Terrapon, N., et al., In Essentials of Glycobiology, 2022, pp. 93-102. The glycocalyx is a highly dynamic structure and remodels in response to different conditions and stimuli. In mammals, fucose is a common monosaccharide present in various forms in glycans present on the glycocalyx. Fucose-containing glycoconjugates have diverse and important roles in development, growth, and signal transduction among other processes. See, Becker et. al., Glycobiology, 2003, 13, 41R-53R. GDP-D-mannose-4,6-dehydratase (GMDS) It has been shown that low fucosylation is a defining characteristic of the healthy LSC glycocalyx. See, Woodward et al., Stem Cell Rep, 2025, 20, 102378. To date, there have been a small number of studies investigating the role of fucosylation in ocular health and disease. Published findings indicates that the functions of fucose in corneal homeostasis are not straightforward, with some studies reporting a protective role for fucose in ocular health, and other studies reporting disease promoting roles for fucose. See, e.g., Isnard et al., Ophthalmologica, 2005, 219, 324-33; Yoon et al., Int J Mol Sci, 2021, 22, 7863; and Kim et al., Cell Death Dis, 2020, 11, 285. Given the variability in outcomes across models, cell types, and methods of fucosylation modulation, prior findings offer no clear precedent for its function in LSCs, making its impact in this context highly uncertain. SUMMARY This disclosure relates, inter alia, to methods for the pharmacological inhibition of fucosylation, which protect human limbal epithelial cells (hLECs) of the cornea, also known as corneal epithelial stem cells, or simply as limbal stem cells (these phrases are used interchangeably herein), from deleterious effects of inflammation and promote limbal stem Attorney Docket No.: 00398-0184WO1 cell viability. To this end, the present disclosure provides methods for preserving the viability of limbal stem cells in a subject in need thereof and in ex vivo cell cultures. The disclosure further provides methods for the treatment, inhibition, or prevention of LSCD, which can develop from, e.g., inflammatory stress associated with ocular diseases and disorders, including but not limited to congenital diseases (e.g., dominantly inherited keratitis, ectodermal dysplasia, aniridia), autoimmune disorders (e.g., Stevens-Johnson syndrome, Sjogren’s syndrome, ocular cicatrical mucous membrane pemphigoid), and infectious diseases (e.g., Herpes simplex keratitis, trachoma). The present disclosure also shows that inhibiting fucosylation can protect susceptible cells, such as limbal stem cells, from cell death in response to inflammatory stress. Thus, the disclosure provides methods of preventing and / or treating LSCD, by, for example, administering one or more inhibitors of fucosylation to the eye of the subject. In addition, the disclosure provides methods for the treatment of ocular diseases and disorders (e.g., inflammatory ocular diseases and disorders). In one aspect, the present disclosure provides methods of treating, inhibiting, or preventing LSCD in a subject in need thereof, the methods including administering to an afflicted eye of the subject a therapeutically effective amount of a fucosylation inhibitor. In some embodiments, the subject is suffering from an ocular disease or disorder. In some embodiments, the stem cell deficiency is associated with an ocular disease or disorder. In some embodiments, the ocular disease or disorder is an autoimmune disease, a congenital disease, an infectious disease, or a traumatic insult, or any ocular disease or disorder described herein. In another aspect, the present disclosure provides methods of treating an inflammatory ocular disease or disorder in a subject in need thereof, the methods including administering to an afflicted eye of the subject a therapeutically effective amount of a fucosylation inhibitor. In some embodiments, the therapeutically effective amount includes a concentration of the fucosylation inhibitor effective to reduce death of limbal stem cells in the afflicted eye. In another aspect, the present disclosure provides methods of enhancing the viability of limbal stem cells in vitro or ex vivo, the methods including adding to a culture of limbal stem cells a fucosylation inhibitor in an amount effective to reduce death of the limbal stem cells. In another aspect, the present disclosure provides fucosylation inhibitors for use in the treatment of an inflammatory ocular disease or disorder in a subject. Attorney Docket No.: 00398-0184WO1 In some embodiments, the fucosylation inhibitor is a compound having Formula (I): (I), or a pharmaceutically acceptable salt thereof, wherein: R1and R2are each independently selected from halo, ORa, SRa, C(O)Rb, C(O)NRcRd, and OP(O)(ORa)2; R3and R4are each independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6haloalkyl, halo, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, C(=NRe1)Rb1, C(=NORa1)Rb1, C(=NRe1)NRc1Rd1, NRc1C(=NRe1)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, S(O)2NRc1Rd1, P(O)(NH2)ORa1, and OP(O)(ORa1)2; wherein said C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with a substituent independently selected from CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, C(=NRe1)Rb1, C(=NORa1)Rb1, C(=NRe1)NRc1Rd1, NRc1C(=NRe1)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, S(O)2NRc1Rd1, P(O)(NH2)ORa1, and OP(O)(ORa1)2; R5is selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C1-6haloalkyl; each Ra, Rc, Rd, Ra1, Rc1, and Rd1is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg; each Rband Rb1is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg; each Reand Re1is independently selected from H, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 Attorney Docket No.: 00398-0184WO1 alkylcarbamyl, di(C1-6alkyl)carbamyl, aminosulfonyl, C1-6alkylaminosulfonyl and di(C1-6alkyl)aminosulfonyl; and each Rgis independently selected from OH, NO2, CN, SC(O)C1-6alkyl, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C1-3alkoxy-C1-3alkyl, C1-3 alkoxy-C1-3 alkoxy, HO-C1-3 alkoxy, HO-C1-3 alkyl, cyano-C1-3 alkyl, H2N-C1-3 alkyl, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6alkylcarbamyl, di(C1-6alkyl)carbamyl, carboxy, C1-6alkylcarbonyl, C1-6alkoxycarbonyl, C1-6alkylcarbonylamino, C1-6alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6alkylaminosulfonylamino, di(C1-6alkyl)aminosulfonylamino, aminocarbonylamino, C1-6alkylaminocarbonylamino, and di(C1-6alkyl)aminocarbonylamino. In some embodiments, R1and R2are each independently selected from OC(O)Rb, halo, ORa, and OP(O)(ORa)2. In some embodiments, R1and R2are each independently selected from OC(O)CH3, F, OH, and OP(O)(OCH2CH2SC(O)CH3)2. In some embodiments, R1is OC(O)CH3, and R2is F. In some embodiments, R3and R4are each independently selected from OC(O)Rb1and ORa1. In some embodiments, R3and R4are each independently selected from OC(O)CH3and OH. In some embodiments, R3and R4are each OC(O)CH3. In some embodiments, R5is selected from C1-6 alkyl, C2-6 alkynyl, and C1-6 haloalkyl. In some embodiments, R5is CH3, CF3, or CCH. In some embodiments, R5is CH3. In some embodiments, the fucosylation inhibitor is any one or more of 2F-Peracetyl- Fucose, A2FF1P, B2FF1P, 6-alkynyl-fucose, 6,6,6-trifluorofucose, Fucostatin II, Fucotrim I, or Fucotrim II. In some embodiments, the fucosylation inhibitor is 2F-peracetyl-Fucose. In certain embodiments, the ocular disease or disorder is an autoimmune disease, a congenital disease, an infectious disease, or a traumatic insult. In some embodiments, the ocular disease or disorder is an autoimmune disease. In some embodiments, the autoimmune disease is Stevens-Johnson syndrome, Sjögren's syndrome, or ocular cicatricial mucous membrane pemphigoid. In some embodiments, the ocular disease or disorder is a congenital disease. In some embodiments, the congenital disease is dominantly inherited keratitis, ectodermal dysplasia, or aniridia. In some embodiments, the ocular disease or disorder is an infectious disease. In some embodiments, the infectious disease is herpes simplex keratitis or trachoma. In some embodiments, the ocular disease or disorder is a traumatic insult. In some embodiments, the traumatic insult is a chemical injury, a thermal injury, or a physical injury. Attorney Docket No.: 00398-0184WO1 In some embodiments, the fucosylation inhibitor is administered topically. In some embodiments, the topical administration including instilling an aliquot of a solution or suspension of the fucosylation inhibitor into the afflicted eye or eyes of the subject. In some embodiments, the aliquot is 1-5 drops of the solution or suspension of the fucosylation inhibitor. In some embodiments, the aliquot is one drop of the solution or suspension of the fucosylation inhibitor. In some embodiments, the solution or suspension is an aqueous solution or suspension. In some embodiments, the solution is a non-aqueous solution. In some embodiments, administering includes intravitreally injecting a solution of the fucosylation inhibitor into the eye of the subject. In some embodiments, the solution is an aqueous solution. In another aspect, the disclosure provides methods of treating LSCD in a subject in need thereof, the methods including culturing limbal epithelial cells in the presence of a fucosylation inhibitor to provide cultured limbal stem cells, and transplanting the cultured limbal stem cells to the eye of the subject. In some embodiments, the transplanting includes using a transplantation technique selected from Conjunctival Limbal Autograft (CLAU), Cultivated Limbal Epithelial Transplantation (CLET), Living-Related Conjunctival Limbal Allograft (LR-CLAL), or Keratolimbal Allograft (KLAL). In some embodiments, the limbal stem cells are cultured ex vivo. In some embodiments, the limbal stem cells are cultured in a base-media composition. In some embodiments, the base-media composition comprises fetal bovine serum (FBS). In some embodiments, the base-media composition comprises about 5% to about 25% FBS by weight. In some embodiments, the base-media composition further comprises hydrocortisone. In some embodiments, the base-media composition comprises about 0.1 μg / mL to about 2 μg / mL hydrocortisone. In some embodiments, the base-media composition further comprises insulin. In some embodiments, the base-media composition comprises about 1 μg / mL to about 15 μg / mL insulin. In some embodiments, the base-media composition further comprises triiodothryonine. In some embodiments, the base-media composition comprises about 1 ng / mL to about 10 ng / mL triiodothryonine. In certain embodiments, the base-media composition further comprises adenine. In some embodiments, the base-media composition comprises about 1 μg / mL to about 100 μg / mL adenine. In some embodiments, the base- media composition further comprises epidermal growth factor. In some embodiments, the base-media composition comprises about 1 μg / mL to about 100 μg / mL epidermal growth factor. Attorney Docket No.: 00398-0184WO1 In another aspect, the disclosure provides methods for reducing limbal stem cell death, the methods including contacting limbal stem cells with a fucosylation inhibitor. In some embodiments, the contacting occurs ex vivo. In some embodiments, the contacting comprises culturing limbal stem cells in the presence of a fucosylation inhibitor. There is a need for new methods to enhance the proliferative capacity of human limbal epithelial stem cells for use in the clinic for the treatment of various ocular diseases. Advantageously, the present disclosure meets this need. In particular, this disclosure demonstrates that the pharmacological inhibition of fucosylation protects limbal stem cells from deleterious effects of inflammation. For example, this disclosure demonstrates that fucose-inhibited limbal stem cells have significantly enhanced viability when challenged with TNF-α + 5Z-7-oxozeaenol (hereinafter referred to as “5Z7”), an inflammatory cell death inducing regiment. Moreover, this disclosure demonstrates that fucosylation inhibited limbal stem cells have greater cumulative population doublings and significantly reduced population doubling time than vehicle control cells continuously exposed to TNF-α+5Z7, highlighting the potential of fucosylation inhibition to preserve limbal cell viability and proliferative abilities in the presence of inflammatory stress. This disclosure therefore demonstrates that inhibitors of fucosylation can be administered to the eye to treat various ocular diseases and disorders characterized by inflammatory stress, including, but not limited to, autoimmune diseases, congenital diseases, infectious diseases, and traumatic insults. As used herein, the term “disorder” is intended to be generally synonymous, and is used interchangeably with, the terms “disease,” “syndrome,” and “condition” (as in medical condition), in that all reflect an abnormal condition of the human or animal body or of one of its parts that impairs normal functioning, and is typically manifested by distinguishing signs and symptoms. Moreover, as used herein, the term “ocular disorder” is used interchangeably with the term “ocular disease,” and refers to a disorder that impairs the normal functioning of the eye. As used herein, the term “subject” can be a vertebrate, such as a mammal, a fish, a bird, a reptile, or an amphibian. Thus, the subject of the methods disclosed herein can be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig, or rodent. The term does not denote a particular age or sex. Thus, adult and newborn subjects, as well as fetuses, whether male or female, are intended to be covered. In one aspect, the subject is a mammal. In one aspect, the subject is a human. Attorney Docket No.: 00398-0184WO1 As used herein, the term “treat,” “treating,” or “treatment” refers to the medical management of a subject with the intent to cure, ameliorate, or stabilize a disease, pathological condition, or disorder. This term includes active treatment, that is, treatment directed specifically toward the improvement of a disease, pathological condition, or disorder, and also includes causal treatment, that is, treatment directed toward removal of the cause of the associated disease, pathological condition, or disorder. In addition, this term includes palliative treatment, that is, treatment designed for the relief of symptoms rather than the curing of the disease, pathological condition, or disorder; preventative treatment, that is, treatment directed to minimizing or partially or completely inhibiting the development of the associated disease, pathological condition, or disorder; and supportive treatment, that is, treatment employed to supplement another specific therapy directed toward the improvement of the associated disease, pathological condition, or disorder. In various aspects, the term covers any treatment of a subject, including a mammal (e.g., a human), and includes: (i) inhibiting the disease, i.e., arresting its development; or (ii) relieving the disease, i.e., causing regression of the disease. A “therapeutically effective amount” when used in connection with a compound or pharmaceutical composition described herein is an amount of one or more pharmaceutically active agent(s) sufficient to produce a beneficial medical result in a subject in need thereof. As used herein, the term “diagnosed or diagnosing” means having been subjected to a physical examination by a person of skill, for example, a physician, and found to have a condition that can be treated by the compounds, compositions, or methods disclosed herein. As used herein, the term “assessing” or “assessed” refers to a form of measurement, including determining if a disease or disorder is present or not, as well as, in some instances, determining the amount of something present and / or determining the change of the amount of something present over time. In some embodiments, assessing a subject can lead to a subject being identified to be in need of treatment for a disorder. As used herein, the terms “administering” and “administration” refer to any method of providing a pharmaceutical preparation to a subject. Such methods are well known to those skilled in the art and include, but are not limited to, oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intravaginal administration, ophthalmic administration, intraaural administration, intracerebral administration, rectal administration, sublingual administration, buccal administration, intraurethral administration, and parenteral administration, including Attorney Docket No.: 00398-0184WO1 injectable such as intravenous administration, intra-arterial administration, intramuscular administration, and subcutaneous administration. Topical administration can include instilling a pharmaceutical preparation (e.g., eye drops) to the eye of the subject. Administration can be continuous or intermittent. In various aspects, a preparation can be administered therapeutically; that is, administered to treat an existing disease or condition. In further various aspects, a preparation can be administered prophylactically; that is, administered for prevention of a disease or condition. The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio. As used herein, the term “pharmaceutically acceptable carrier” relates to nontoxic ingredients which are defined as vehicles commonly used to formulate pharmaceutical compositions for animal or human administration. Such carriers may include, however are not limited to, buffering agents, solubilizing agents, stabilizing agents or taste additives. The present invention also includes pharmaceutically acceptable salts of the compounds described herein. As used herein, “pharmaceutically acceptable salts” refers to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts of the present invention include the non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two. Lists of suitable salts are found in Remington’s Pharmaceutical Sciences, 17thed., Mack Publishing Company, Easton, Pa., 1985, p. 1418 and Journal of Pharmaceutical Science, 66, 2 (1977), each of which is incorporated herein by reference in its entirety. Attorney Docket No.: 00398-0184WO1 At various places in the present specification, substituents of compounds recited herein are disclosed in groups or in ranges. It is specifically intended that the methods described herein include each and every individual subcombination of the members of such groups and ranges. For example, the term “C1-6alkyl” is specifically intended to individually disclose methyl, ethyl, C3 alkyl, C4 alkyl, C5 alkyl, and C6 alkyl. For compounds disclosed herein in which a variable appears more than once, each variable can be a different moiety independently selected from the group defining the variable. For example, where a structure is described having two R groups that are simultaneously present on the same compound, the two R groups can represent different moieties independently selected from the group defined for R. As used herein, the term “substituted” means that a hydrogen atom is replaced by a non-hydrogen group. It is to be understood that substitution at a given atom is limited by valency. As used herein, the phrase “optionally substituted” means unsubstituted or substituted. As used herein, the term “Ci-j,” where I and j are integers, employed in combination with a chemical group, designates a range of the number of carbon atoms in the chemical group with i-j defining the range. For example, C1-6alkyl refers to an alkyl group having 1, 2, 3, 4, 5, or 6 carbon atoms. As used herein, the term “alkyl,” employed alone or in combination with other terms, refers to a saturated hydrocarbon group that may be straight-chain or branched. In some embodiments, the alkyl group contains 1 to 7, 1 to 6, 1 to 4, or 1 to 3 carbon atoms. Examples of alkyl moieties include, but are not limited to, chemical groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methyl-1-butyl, 3-pentyl, n-hexyl, 1,2,2-trimethylpropyl, n-heptyl, and the like. In some embodiments, the alkyl group is methyl, ethyl, or propyl. As used herein, “alkenyl,” employed alone or in combination with other terms, refers to an alkyl group having one or more carbon-carbon double bonds. In some embodiments, the alkenyl moiety contains 2 to 6 or 2 to 4 carbon atoms. Examples of alkenyl groups include, but are not limited to, ethenyl, n-propenyl, isopropenyl, n-butenyl, sec-butenyl, and the like. As used herein, “alkynyl,” employed alone or in combination with other terms, refers to an alkyl group having one or more carbon-carbon triple bonds. Examples of alkynyl Attorney Docket No.: 00398-0184WO1 groups include, but are not limited to, ethynyl, propyn-1-yl, propyn-2-yl, and the like. In some embodiments, the alkynyl moiety contains 2 to 6 or 2 to 4 carbon atoms. As used herein, “halo” or “halogen”, employed alone or in combination with other terms, includes fluoro, chloro, bromo, and iodo. In some embodiments, halo is F or Cl. As used herein, the term “haloalkyl,” employed alone or in combination with other terms, refers to an alkyl group having up to the full valency of halogen atom substituents, which may either be the same or different. In some embodiments, the halogen atoms are fluoro atoms. In some embodiments, the alkyl group has 1 to 6 or 1 to 4 carbon atoms. Examples of haloalkyl groups include CF3, C2F5, CHF2, CCl3, CHCl2, C2Cl5, and the like. As used herein, the term “alkoxy,” employed alone or in combination with other terms, refers to a group of formula -O-alkyl. Examples of alkoxy groups include methoxy, ethoxy, propoxy (e.g., n-propoxy and isopropoxy), t-butoxy, and the like. In some embodiments, the alkyl group has 1 to 6 or 1 to 4 carbon atoms. As used herein, “haloalkoxy,” employed alone or in combination with other terms, refers to a group of formula -O-(haloalkyl). In some embodiments, the alkyl group has 1 to 6 or 1 to 4 carbon atoms. An example of a haloalkoxy group is -OCF3. As used herein, “amino,” employed alone or in combination with other terms, refers to NH2. As used herein, the term “alkylamino,” employed alone or in combination with other terms, refers to a group of formula -NH(alkyl). In some embodiments, the alkylamino group has 1 to 6 or 1 to 4 carbon atoms. Examples of alkylamino groups include methylamino, ethylamino, propylamino (e.g., n-propylamino and isopropylamino), and the like. As used herein, the term “dialkylamino,” employed alone or in combination with other terms, refers to a group of formula -N(alkyl)2. Examples of dialkylamino groups include dimethylamino, diethylamino, dipropylamino (e.g., di(n-propyl)amino and di(isopropyl)amino), and the like. In some embodiments, each alkyl group independently has 1 to 6 or 1 to 4 carbon atoms. The compounds described herein can be asymmetric (e.g., having one or more stereocenters). All stereoisomers, such as enantiomers and diastereomers, are intended unless otherwise indicated. Compounds of the present invention that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically inactive starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Geometric Attorney Docket No.: 00398-0184WO1 isomers of olefins, C=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present invention may be isolated as a mixture of isomers or as separated isomeric forms. The compounds described herein also include tautomeric forms, which result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Examples of prototropic tautomers include ketone–enol pairs, amide-imidic acid pairs, lactam–lactim pairs, enamine–imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, for example, 1H- and 3H-imidazole, 1H-, 2H- and 4H- 1,2,4-triazole, 1H- and 2H- isoindole, and 1H- and 2H-pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution. The compounds described herein also include all isotopes of atoms occurring in the intermediates or final compounds. Isotopes include those atoms having the same atomic number but different mass numbers. For example, isotopes of hydrogen include tritium and deuterium. In some embodiments, the compounds of the invention include at least one deuterium atom. The term “compound,” as used herein, is meant to include all stereoisomers, geometric isomers, tautomers, and isotopes of the structures depicted, unless otherwise specified. All compounds, and pharmaceutically acceptable salts thereof, can be found together with other substances such as water and solvents (e.g., in the form of hydrates and solvates) or can be isolated. In some embodiments, the compounds described herein, or salts thereof, are substantially isolated. By “substantially isolated” is meant that the compound is at least partially or substantially separated from the environment in which it was formed or detected. Partial separation can include, for example, a composition enriched in the compounds of the invention. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of the compounds of the invention, or salt thereof. Methods for isolating compounds and their salts are routine in the art. Attorney Docket No.: 00398-0184WO1 In this application, the use of the singular includes the plural unless specifically stated otherwise. It must be noted that, as used in the specification, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. In this application, the use of “or” means “and / or” unless stated otherwise. Furthermore, use of the term “including” as well as other forms, such as “include,” “includes,” and “included,” are not limiting. As used herein, ranges and amounts can be expressed as "about" a particular value or range. About also includes the exact amount. Hence "about 5 µl" means "about 5 µl" and also "5 µl." Generally, the term "about" includes an amount that would be expected to be within experimental error. Unless specifically stated or apparent from context, as used herein, the term "about" in reference to a number or range of numbers is understood to mean the stated number and numbers + / -10% thereof, or 10% below the lower listed limit and / or 10% above the higher listed limit for the values listed for a range. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the claimed subject matter belongs. It is to be understood that the detailed description provides examples and explanations only, which are not restrictive of any subject matter claimed. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. Although various features of the disclosure may be described in the context of a single embodiment, the features may also be provided separately or in any suitable combination. Conversely, although the disclosure may be described herein in the context of separate embodiments for clarity, the disclosure may also be implemented in a single embodiment. The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. Other features and advantages of the methods and compositions of the disclosure will be apparent from the following detailed description, and from the claims. Attorney Docket No.: 00398-0184WO1 BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1A is a graph of qPCR data assessing the levels of tissue specific transplantation antigen P35B (TSTA3), also known as GDP-L-fucose synthetase, in limbal stem cells treated with 0 ng / ml, 100 ng / ml or 1,000 ng / ml TNF-α for 24 hours. FIG. 1B is a graph of qPCR data assessing the levels of GDP-D-mannose-4,6- dehydratase (GMDS) in limbal stem cells treated with 0 ng / ml, 100 ng / ml or 1,000 ng / ml TNF-α for 24 hours. FIG. 2A is a microscopic image of the limbal stem cell culture, tagged with Aleuria Aurantia Lectin (AAL)-fluorescein, in the presence of a DMSO vehicle (control). The figure shows multiple cells glowing white. FIG. 2B is a microscopic image of the limbal stem cell culture, tagged with AAL- fluorescein, in the presence of the fucosylation inhibitor 2FF. The fact that hardly any of the cells show a white glow and the figure is mostly black demonstrates that the inhibitor is working. FIG. 3A depicts a cell death curve over a 28-hour period post-exposure to a high dose of TNFα+5z7, in the presence and absence of the fucosylation inhibitor 2FF. FIG. 3B is a representative image from hour 17 of primary limbal cells challenged with inflammatory molecules TNFα+5z7, in the absence of the fucosylation inhibitor 2FF. FIG. 3C is a representative image from hour 17 of primary limbal cells challenged with inflammatory molecules TNFα+5z7, in the presence of the fucosylation inhibitor 2FF. The fact that FIG. 3B, which shows the results without the inhibitor, has significant white staining, and that FIG. 3C, which shows the results with the inhibitor, has hardly any white staining again demonstrates that the inhibitor is effective. FIG. 4A is a graph that depicts qPCR array data showing relative expression of 84 cell death and / or cell survival related genes in limbal stem cells cultured for 3 days with or without 2FF (DMSO control) then treated with TNF-α+5Z7 for 0 hours (unstimulated). FIG. 4B is a graph that depicts qPCR array data showing relative expression of 84 cell death and / or cell survival related genes in limbal stem cells cultured for 3 days with or without 2FF (DMSO control) then treated with TNF-α+5Z7 for 4 hours. FIG. 4C is a graph that depicts qPCR array data showing relative expression of 84 cell death and / or cell survival related genes in limbal stem cells cultured for 3 days with or without 2FF (DMSO control) then treated with TNF-α+5Z7 for 24 hours. Genes represented by shaded-in circles indicate statistically significant fold change values, with the pro-survival Attorney Docket No.: 00398-0184WO1 genes BCL2, BAG3 and BIRC3 being ≥ 1.5 fold change higher (p-value >.05) in the 2FF treated group. FIG. 5A is a graph showing the cumulative population doubling of limbal stem cells cultured with low-dose TNFα+5Z7 either in the presence or absence of 2FF in a first donor. FIG. 5B is a graph showing the cumulative population doubling of limbal stem cells cultured with low-dose TNFα+5Z7 either in the presence or absence of 2FF in a second donor. FIG. 5C is a graph showing the cumulative population doubling of limbal stem cells cultured with low-dose TNFα+5Z7 either in the presence or absence of 2FF in a third donor. FIG. 6A is a bar graph that shows the population doubling time across a first passage of limbal stem cells continuously exposed to low doses of TNF+527 and either a DMSO vehicle (control) or 2FF. FIG. 6B is a bar graph that shows the population doubling time across a second passage of limbal stem cells continuously exposed to low doses of TNF+527 and either a DMSO vehicle (control) or 2FF. FIG. 6C is a bar graph that shows the population doubling time across a third passage of limbal stem cells continuously exposed to low doses of TNF+527 and either a DMSO vehicle (control) or 2FF. FIG. 6D is a bar graph that shows the population doubling time across a fourth passage of limbal stem cells continuously exposed to low doses of TNF+527 and either a DMSO vehicle (control) or 2FF. FIG. 6E is a bar graph that shows the population doubling time across a fifth passage of limbal stem cells continuously exposed to low doses of TNF+527 and either a DMSO vehicle (control) or 2FF. FIG. 7A is a schematic of a modeled structure of TNFR1 (grey ribbon structure) with labeled predicted N-glycosylation sites (dark gray spheres) and TNF (lighter gray space filled model). FIG. 7B is a schematic of a modeled structure of TNFR1, including one N- glycosylation site (N145) that is in close spatial proximity to the TNF-TNFR1 binding site. FIG. 7C is a schematic of a model of overlaid structures of TNFR1 and TNFR2 with predicted N glycosylation sites highlighted in dark gray and light gray spheres respectively. Attorney Docket No.: 00398-0184WO1 DETAILED DESCRIPTION OF THE DISCLOSURE The cornea is a transparent and avascular tissue located at the front of the eye, acting as a protective barrier against environmental threats while contributing significantly to refraction and the eye’s optical system. Toward the peripheral boundary of the cornea lies a specialized region called the limbus. The limbus, a transitional zone between the peripheral cornea and the anterior sclera, possesses a population of stem cells that are at the forefront of maintaining and repairing the cornea, which are referred to as limbal stem cells. The health of the cornea hinges upon continuous renewal of its epithelium by limbal stem cells. Dysfunction of limbal stem cells is increasingly recognized as a component of numerous ocular surface diseases, leading to LSCD. See Sejpal, K., et al., Middle East African Journal of Ophthalmology, 2013, 20(1), 5–10. LSCD is characterized by the dysfunction or loss of LSCs. A key feature in the development of LSCD is ocular surface inflammation. In this context it is therefore of paramount importance to understand factors that regulate LSC survival in the face of inflammation. It has been observed that the glycocalyx of human LSCs derived from healthy cadaveric corneal donors are distinguished by a low abundance of the monosaccharide fucose. A small collection of studies has illustrated that some death receptors are fucosylated and that fucosylation affects their signaling properties. See, e.f., Yu, H., et al., Arthritis research & therapy, 2022, 24(1), 93; Lin, S., et al., Cell Death & Disease, 2021, 12(12), 1124; and Zhang, B., et al., The FEBS Journal, 2019, 286(3), 555–571. The present disclosure demonstrates, inter alia, that pharmacological inhibition of fucosylation protects limbal stem cells from deleterious effects of inflammation. It is shown that fucose-inhibited limbal stem cells have significantly enhanced viability when challenged with TNF-α+5Z7, an inflammatory cell death inducing regiment. Moreover, it is shown that fucosylation inhibited limbal stem cells have greater cumulative population doublings and significantly reduced population doubling time than vehicle control cells continuously exposed to TNF-α+5Z7, highlighting the potential of fucosylation inhibition to preserve limbal cell viability and proliferative abilities in the presence of inflammatory stress. In addition, this disclosure provides methods of fucosylation inhibition to promote limbal progenitor cell viability, for example, in vitro or ex vivo, and methods of treating an ocular disease or disorder in a subject in need thereof, the methods including administering to the eye of the subject a therapeutically effective amount of a fucosylation inhibitor. Also provided herein are methods of treating a limbal stem cell deficiency in a subject in need Attorney Docket No.: 00398-0184WO1 thereof, the methods including culturing limbal cells in the presence of a fucosylation inhibitor to provide cultured limbal cells, and transplanting the cultured limbal cells into the eye of the subject. Inflammation and cell death are major components in the pathophysiology of ocular diseases / conditions including, but not limited to, congenital diseases (e.g., dominantly inherited keratitis, ectodermal dysplasia, aniridia), autoimmune disorders (e.g., Stevens- Johnson syndrome, Sjogren’s syndrome, ocular cicatrical mucous membrane pemphigoid), and infectious diseases (e.g., Herpes simplex keratitis, trachoma). Further, it has been shown that inflammation increases fucosylation. The present disclosure demonstrates that this increase in fucosylation is associated with a greater susceptibility to cell death. The present disclosure also demonstrates that inhibiting fucosylation protects limbal stem cells from death in inflammatory conditions, which can lead to limbal stem cell deficiency and can result in blindness. Methods of Inhibiting Fucosylation to Preserve Limbal Stem Cell Viability and Treat Ocular Diseases The inhibition of fucosylation can be used to preserve limbal stem cell viability. Thus, fucosylation inhibitors can be used to treat or prevent limbal stem cell deficiency in a subject in need thereof. Limbal stem cell deficiency can be caused by or associated with several ocular diseases and disorders, including but not limited to an autoimmune disease, a congenital disease, an infectious disease, or a traumatic insult, or any ocular disease or disorder described herein. Thus, a fucosylation inhibitor can be administered to a subject suffering from an ocular disease or disorder, to prevent the development of a limbal stem cell deficiency, which can lead to blindness. In one aspect, the present disclosure provides methods of preserving the viability of limbal stem cells in a subject in need thereof, the methods including administering to an eye of the subject a therapeutically effective amount of a fucosylation inhibitor. In some embodiments, the subject is suffering from an ocular disease or disorder. In some embodiments, the ocular disease or disorder is an autoimmune disease, a congenital disease, an infectious disease, or a traumatic insult, or any ocular disease or disorder described herein. In another aspect, the present disclosure provides methods of preventing limbal stem cell deficiency in a subject in need thereof, the method including administering to an eye of the subject a therapeutically effective amount of a fucosylation inhibitor. In some Attorney Docket No.: 00398-0184WO1 embodiments, the subject is suffering from an ocular disease or disorder. In some embodiments, the stem cell deficiency is associated with an ocular disease or disorder. In some embodiments, the ocular disorder is an autoimmune disease, a congenital disease, an infectious disease, or a traumatic insult, or any ocular disease or disorder described herein. Ocular diseases and disorders that can lead to or be associated with limbal stem cell deficiency, include, but are not limited to, autoimmune diseases, congenital diseases, infectious diseases, and traumatic insults. Examples of autoimmune diseases that can be treated by the methods disclosed herein include, but are not limited to, Stevens-Johnson syndrome, Sjögren's syndrome, and ocular cicatricial mucous membrane pemphigoid. Examples of congenital diseases that can lead to or be associated with limbal stem cell deficiency include, but are not limited to, dominantly inherited keratitis, ectodermal dysplasia, and aniridia. Examples of infectious diseases that can lead to or be associated with limbal stem cell deficiency include, but are not limited to, herpes simplex keratitis and trachoma. Examples of traumatic insults that can lead to or be associated with limbal stem cell deficiency include, but are not limited to, a chemical injury, a thermal injury, and a physical injury. To evaluate how effectively a fucosylation inhibitor preserves limbal stem cells (LSCs), clinical methods can be used to quantify LSC presence and function. Two possible approaches for this assessment are impression cytology and optical coherence tomography (OCT) imaging. Impression cytology is a minimally invasive technique in which a sterile cellulose acetate or polyvinylidene fluoride (PVDF) membrane is gently pressed onto the ocular surface and peeled away to capture adherent cells. The membrane is then processed for immunohistochemical analysis to detect the presence of key LSC markers. Staining ΔNp63 isoform provides a measure of LSC abundance, as this transcription factor is highly expressed in basal limbal epithelial cells with stem-like properties. ABCG2, an ATP-binding cassette transporter associated with stem cell self-renewal, further distinguishes LSCs from transient amplifying cells. A reduction in these markers following injury or disease indicates LSC depletion, while their retention in fucosylation inhibitor-treated eyes would support the notion that the therapy preserves LSC populations. Additionally, the absence of goblet cells in the corneal / limbal epithelium would indicate a preserved LSC population. Optical coherence tomography (OCT) is a non-invasive imaging technique that enables high-resolution visualization of the limbal niche. Anterior segment OCT (AS-OCT) Attorney Docket No.: 00398-0184WO1 provides cross-sectional imaging of the limbal region, allowing for an assessment of limbal thickness and epithelial integrity. In LSCD, AS-OCT often reveals limbal thinning, epithelial irregularities, and increased light reflectivity due to fibrosis or conjunctivalization. Changes in limbal architecture can be tracked over time to determine whether treatment preserves structural integrity. OCT angiography can further provide insight into limbal vasculature, as LSCD is often accompanied by pathological neovascularization. A reduction in limbal neovascularization and the preservation of normal limbal epithelial structure following treatment would indicate a protective effect of the drug. In an ex vivo limbal epithelial culture setting, flow cytometry and immunocytochemistry using LSC-specific markers—such as p63α, ABCG2, and CK15— allow for the identification and quantification of stem-like populations. Colony-forming efficiency (CFE) assays provide a functional assessment by measuring the ability of cultured cells to proliferate long-term. Moreover, the inhibition of fucosylation can be used to treat ocular diseases and disorders that are characterized by the dysfunction of limbal stem cells and / or pathologies that destroy limbal stem cells. Ocular surface inflammation is a common factor in many ocular diseases and disorders, and it is established that this inflammation can adversely affect limbal stem cells. Therefore, the use of fucose-inhibitors to preserve limbal stem cell viability, and by extension, function, may have a beneficial therapeutic impact across diverse ocular pathologies. In another aspect, the present disclosure provides methods of treating an ocular disorder in a subject in need thereof, the method including administering to an afflicted eye of the subject a therapeutically effective amount of a fucosylation inhibitor. In another aspect, the present disclosure provides methods of treating an inflammatory ocular disorder in a subject in need thereof, the method including administering to an afflicted eye of the subject a therapeutically effective amount of a fucosylation inhibitor, wherein the fucosylation inhibitor is any one or more of 2F-Peracetyl-Fucose, A2FF1P, B2FF1P, 6-alkynyl-fucose, 6,6,6-trifluorofucose, Fucostatin II, Fucotrim I, or Fucotrim II. Ocular diseases and disorders that can be treated by the methods described herein include, but are not limited to, autoimmune diseases, congenital diseases, infectious diseases, and traumatic insults. Examples of autoimmune diseases that can be treated by the methods disclosed herein include, but are not limited to, Stevens-Johnson syndrome, Sjögren's syndrome, and ocular cicatricial mucous membrane pemphigoid. Examples of congenital Attorney Docket No.: 00398-0184WO1 diseases that can be treated by the methods disclosed herein include, but are not limited to, dominantly inherited keratitis, ectodermal dysplasia, and aniridia. Examples of infectious diseases that can be treated by the methods disclosed herein include, but are not limited to, herpes simplex keratitis and trachoma. Examples of traumatic insults that can be treated by the methods disclosed herein include, but are not limited to, a chemical injury, a thermal injury, and a physical injury. The fucosylation inhibitors used in the methods disclosed herein can be administered topically, e.g., as a fucosylation inhibitor drug suspended in any one of a plurality of different ophthalmic solutions, formulated according to standard pharmaceutical manufacturing practices as eye drops. Topical administration can target the cornea, but in certain embodiments can target the conjunctival sac, and / or eyelid. In some embodiments, the administering comprises instilling an aliquot of a solution or suspension of the fucosylation inhibitor onto the eyes of the subject. In some embodiments, the aliquot is one, two, three, four, or five drops, or more, of the solution or suspension of the fucosylation inhibitor. In some embodiments, the aliquot is one to four drops, one to three drops, or, one to two drops of the solution or suspension of the fucosylation inhibitor. In some embodiments, the aliquot is two to three, two to four, or two to five drops of the solution or suspension of the fucosylation inhibitor. In some embodiments, the solution or suspension is an aqueous solution or suspension of the fucosylation inhibitor. In some embodiments, the solution or suspension is a nonaqueous solution or suspension of the fucosylation inhibitor. In some embodiments, the nonaqueous solution or suspension comprises ethanol. In some embodiments, the nonaqueous solution or suspension comprises perfluorobutylpentane. In some embodiments, the solution or suspension comprises an oil based solvent. In some embodiments, the solution or suspension comprises an emulsion of an oil in water. In some embodiments, the solution or suspension comprises gel systems, hydrogels, nanoparticles, liposomes, cationic emulsions, or penetration colloidal carriers. In some embodiments, the solution or suspension comprises about 0.0005% to about 5.00% of the fucosylation inhibitor by weight. In some embodiments, the solution or suspension comprises about 0.0025% to about 5.00% of the fucosylation inhibitor by weight. In some embodiments, the solution or suspension comprises about 0.0025% to about 2.5% of the fucosylation inhibitor by weight. In some embodiments, the solution or suspension comprises about 0.025% to about 5.00% of the fucosylation inhibitor by weight. In some Attorney Docket No.: 00398-0184WO1 embodiments, the solution or suspension comprises about 0.01% to about 5.00% of the fucosylation inhibitor by weight. In some embodiments, the solution or suspension comprises about 0.01% to about 3.00% of the fucosylation inhibitor by weight. In some embodiments, the solution or suspension comprises about 0.01% to about 1.00% of the fucosylation inhibitor by weight. In some embodiments, the solution or suspension comprises about 0.025% to about 2.00% of the fucosylation inhibitor by weight. In some embodiments, the solution or suspension comprises about 0.025% to about 1.00% of the fucosylation inhibitor by weight. In some embodiments, the fucosylation inhibitor is present in the suspension or solution at a concentration of about 1 - 100,000 micromolar. In some embodiments, the fucosylation inhibitor is present in the suspension or solution at a concentration of about 1 - 10,000 micromolar. In some embodiments, the fucosylation inhibitor is present in the suspension or solution at a concentration of about 10 - 10,000 micromolar. In some embodiments, the fucosylation inhibitor is present in the suspension or solution at a concentration of about 10 - 1,000 micromolar. In some embodiments, the fucosylation inhibitor is present in the suspension or solution at a concentration of about 10 - 100 micromolar. In some embodiments, the fucosylation inhibitor is present in the suspension or solution at a concentration of about 100 - 10,000 micromolar. In some embodiments, the fucosylation inhibitor is present in the suspension or solution at a concentration of about 100 - 1,000 micromolar. In some embodiments, the fucosylation inhibitor is present in the suspension or solution at a concentration of about 1,000 - 10,000 micromolar. In some embodiments, the fucosylation inhibitor is first administered to the subject within 24, 18, 12, 8, 6, 4, 2, or 1 hours following an acute injury (e.g., chemical burns) to the patient. In some embodiments, the fucosylation inhibitor is administered for a period of 1, 2, 4, 6, 8, 10, 12, 14, or 16 weeks following an acute injury. In some embodiments, the fucosylation inhibitor is administered for a period of at least 1-16 weeks following an acute injury. In some embodiments, the fucosylation inhibitor is administered for a period of at least 2-16 weeks following an acute injury. In some embodiments, the fucosylation inhibitor is administered for a period of 4-16 weeks following an acute injury. In some embodiments, the fucosylation inhibitor is administered for a period of at least 8-16 weeks following an acute injury. In some embodiments, the fucosylation inhibitor is administered for a period of at least 12-16 weeks following an acute injury. In some embodiments, the fucosylation inhibitor is administered for a period of at least 4-16 weeks following an acute injury. In Attorney Docket No.: 00398-0184WO1 some embodiments, the fucosylation inhibitor is administered for a period of at least 4-12 weeks following an acute injury. In some embodiments, the fucosylation inhibitor is administered for a period of at least 4-8 weeks following an acute injury. In some embodiments, the fucosylation inhibitor is administered for a period of at least 1-2 weeks following an acute injury. In some embodiments, the fucosylation inhibitor is administered for a period of at least 1-4 weeks following an acute injury. In some embodiments, the fucosylation inhibitor is administered to the subject prior to a surgical procedure (e.g., limbal autografts or keratoplasty) on the eye(s) of a subject. In some embodiments, the fucosylation inhibitor is administered for a period of 1, 2, 4, 6, 8, 10, 12, 14, or 16 weeks prior to the surgical procedure. In other instances, the fucosylation inhibitors may be administered by local application (e.g. injection subconjunctivally, intracamerally, intravitreally, subtenon, subretinally, subchoroidally, or suprachoroidally). In some embodiments, the administering comprises injecting a solution of the fucosylation inhibitor into the eye of the subject. In some embodiments, the administering comprises intravitreally injecting a solution of the fucosylation inhibitor to the eye of the subject. In some embodiments, the injecting is performed on the cornea of the eye. In some embodiments, the injecting is performed on the cornea conjunctival sac of the eye. In some embodiments, the solution of the fucosylation inhibitor is an aqueous solution. Also provided herein are methods of transplanting limbal stem cells to a subject in need thereof to treat a limbal stem cell deficiency in a subject in need thereof. The methods of transplanting the limbal stem cells can include culturing limbal stem cells in the presence of a fucosylation inhibitor to provide cultured limbal cells, and transplanting the cultured limbal cells into the eye of the subject. The methods of transplanting the limbal stem cells can further include storing limbal cells in the presence of a fucosylation inhibitor to provide cultured limbal cells, and transplanting the cultured limbal cells into the eye of the subject. The limbal stem cells can be collected from a donor or from the subject. Collected tissue / cells should be stored in an appropriate storage buffer containing a fucosylation inhibitor (e.g., 2FF at 100 µM). Also provided herein is the use of fucosylation inhibitors for the preservation and storage of limbal epithelial cells in combination with any of the existing storage media currently employed for this purpose, including, but not limited to, Optisol-GS, Dulbecco's Modified Eagle Medium (DMEM), Minimum Essential Medium (MEM), and Attorney Docket No.: 00398-0184WO1 HypoThermosol, and serum-free media formulations thereof. The storage media may further comprise cryoprotectants such as dimethyl sulfoxide (DMSO) at concentrations ranging from 1–15%, hydroxyethyl starch (HES) at 1–10%, or trehalose at 10–50 mM; growth factors such as epidermal growth factor (EGF) at 10–100 ng / mL or insulin-transferrin-selenium (ITS) at 1–10 μg / mL; antioxidants such as glutathione at 1–10 mM or ascorbic acid at 0.1–1 mM; anti-apoptotic agents such as ROCK inhibitors (e.g., Y-27632) at 5–50 μM; osmotic agents such as chondroitin sulfate at 1–5% or dextran at 1–10%; and antibiotics such as gentamicin at 50–200 μg / mL or streptomycin at 50–500 μg / mL. Fucose inhibitors can be applied with any of these media formulations, whether for short-term hypothermic storage or long-term cryopreservation, ensuring the maintenance of limbal epithelial stem cell viability, integrity, and regenerative potential. In some embodiments, the limbal tissue / cells are cultured in an appropriate culture media containing a fucosylation inhibitor (e.g., 2FF at 100 µM). In some embodiments, the limbal stem cells are cultured in a base-media composition containing a fucosylation inhibitor. A base-media composition can include the following components: DMEM GlutaMAX™:F12 with 10% fetal bovine serum (“FBS”), 0.4 μg / mL hydrocortisone, 5 μg / mL insulin, 1.4 ng / mL triiodothyronine, 24 μg / mL adenine, 10 ng / mL epidermal growth factor and 1% antibiotic–antimycotic. In some embodiments, the base-media composition includes from about 0 to about 25%, e.g., 5, 10, 15, 20, or 25% of FBS by weight. In some embodiments, the base-media composition includes hydrocortisone at a concentration from about 0 to about 2 μg / mL, e.g., .5, 1.0, 1.5, or 2.0 μg / mL. In some embodiments, the base- media composition includes insulin at a concentration from about 0 to about 15 μg / mL, e.g., 2.5, 5.0, 7.5, 10.0, 12.5, or 15.0 μg / mL. In some embodiments, the base-media composition includes triiodothryonine at a concentration from about 0 to about 10 ng / mL, e.g., 2, 4, 6, 8, or 10 ng / mL. In some embodiments, the base-media composition includes adenine at a concentration from about 0 to about 100 μg / mL, e.g., 10, 20, 30, 40 , 50, 60, 70, 80, 90, or 100 μg / mL. In some embodiments, the base-media composition includes epidermal growth factor at a concentration from about 0 to about 100 μg / mL, e.g., 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 μg / mL. In some embodiments, the base-media composition includes about 0% to about 8%, e.g., 1, 2, 3, 4, 5, 6, 7, or 8%, of an antibiotic-antimycotic by weight. In other embodiments, the base-media composition can include, for example, Dulbecco's Modified Eagle Medium / Nutrient Mixture F-12 (DMEM:F12), Minimum Essential Medium (MEM), Roswell Park Memorial Institute medium (RMPI), serum-free Attorney Docket No.: 00398-0184WO1 media (SFM), or Keratinocyte-SFM (KSFM). In other embodiments, the base-media composition can include growth factors and cytokines, including but not limited to Basic Fibroblast Growth Factor (bFGF), Epidermal Growth Factor (EGF), Insulin-like Growth Factor (IGF), Transforming Growth Factor-beta (TGF-β), and Leukemia Inhibitory Factor (LIF). The base-media composition can further include serum or serum replacement, hormones (e.g., insulin, triiodothryonine, dexamethasone, estradiol, or progesterone), vitamins and minerals (e.g., Vitamin C, Vitamin E, folic acid, selenium, zinc), and extracellular matrix components (e.g., laminin, collagen, and fibronectin). The cultured limbal cells can be administered to the eye, for example, at the surface of the eye. Cells may be administered in the presence or absence of a carrier, such as amniotic membrane, Fibrin Gel, Collagen Scaffolds, Polymeric Scaffolds, bio-resorbable carriers such as poly(lactic acid) (PLA) or poly(glycolic acid) (PGA), donor corneal tissue or corneal stromal lenticules carriers. In some embodiments, from about 1 cell to 107cells are administered. The transplantation can further include the post-operative and / or pre-operative use of an ophthalmologic solution containing a fucosylation inhibitor to enhance the viability, engraftment and subsequent proliferation of transplanted limbal cells. In some embodiments, the transplanting comprises using a transplantation technique selected from Conjunctival Limbal Autograft (CLAU), Cultivated Limbal Epithelial Transplantation (CLET), Living-Related Conjunctival Limbal Allograft (LR-CLAL) and Keratolimbal Allograft (KLAL). Techniques for the transplantation of limbal cells are well described in the art, for example, in Moshirfar M, Thomson AC, Ronquillo Y. Limbal Epithelial Transplant. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. In some embodiments, the subject in need of the disclosed methods is a subject diagnosed with a limbal stem cell deficiency. In some embodiments, the subject in need of the disclosed methods is a subject in need of limbal stem cell transplantation. Fucosylation Inhibitors Inhibition of fucosylation enhances the survival of limbal epithelial cells when challenged with death-inducing inflammatory molecules. Inhibition of fucosylation is achieved by exposing cells to, or incubating cells with, fucosylation inhibitors, such as fucose analogs, that decrease the activity of specific intracellular proteins in the fucosylation Attorney Docket No.: 00398-0184WO1 pathway. Described below are fucosylation inhibitors that can be used in the methods disclosed herein. Certain fucosylation inhibitors are known in the art, see, for example, Pijnenborg et al., “Cellular Fucosylation Inhibitors Based on Fluorinated Fucose-1-phosphates,” Chemistry, 2021; 27(12):4022-4027; Al-Shareffi et al., “6-alkynyl fucose is a bioorthogonal analog for O-fucosylation of epidermal growth factor-like repeats and thrombospondin type-1 repeats by protein O-fucosyltransferases 1 and 2,” Glycobiology, 2013; 23(2):188-98; and Scheper et al., “Understanding glycosylation: Regulation through the metabolic flux of precursor pathways,” Biotechnol Adv., 2023; 67:108184. In some embodiments, the fucosylation inhibitor is a compound having Formula (I): (I), or a pharmaceutically acceptable salt thereof, wherein: R1and R2are each independently selected from halo, ORa, SRa, C(O)Rb, C(O)NRcRd, and OP(O)(ORa)2; R3and R4are each independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, C(=NRe1)Rb1, C(=NORa1)Rb1, C(=NRe1)NRc1Rd1, NRc1C(=NRe1)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, S(O)2NRc1Rd1, P(O)(NH2)ORa1, and OP(O)(ORa1)2; wherein said C1-6alkyl, C2-6alkenyl, and C2-6alkynyl are each optionally substituted with a substituent independently selected from CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, C(=NRe1)Rb1, C(=NORa1)Rb1, C(=NRe1)NRc1Rd1, NRc1C(=NRe1)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, S(O)2NRc1Rd1, P(O)(NH2)ORa1, and OP(O)(ORa1)2; Attorney Docket No.: 00398-0184WO1 R5is selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C1-6haloalkyl; each Ra, Rc, Rd, Ra1, Rc1, and Rd1is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6alkynyl and C1-6haloalkyl; wherein said C1-6alkyl, C2-6alkenyl and C2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg; each Rband Rb1is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg; each Reand Re1is independently selected from H, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6alkyl)carbamyl, aminosulfonyl, C1-6alkylaminosulfonyl and di(C1-6alkyl)aminosulfonyl; and each Rgis independently selected from OH, NO2, CN, SC(O)C1-6 alkyl, halo, C1-6 alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C1-3alkoxy-C1-3alkyl, C1-3alkoxy-C1-3alkoxy, HO-C1-3alkoxy, HO-C1-3alkyl, cyano-C1-3alkyl, H2N-C1-3alkyl, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6alkoxycarbonyl, C1-6alkylcarbonylamino, C1-6alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6alkyl)aminocarbonylamino. In some embodiments, R1and R2are each independently selected from OC(O)Rb, halo, ORa, and OP(O)(ORa)2. In some embodiments, R1is OC(O)CH3, and R2is F. In some embodiments, R1is selected from OC(O)Rb, halo, ORa, and OP(O)(ORa)2. In some embodiments, R1is selected from OC(O)Rb, ORa, and OP(O)(ORa)2. In some embodiments, R1is OC(O)CH3. In some embodiments, R1is ORa. In some embodiments, R1is OP(O)(ORa)2. In some embodiments, R2is selected from OC(O)CH3, F, OH, and OP(O)(OCH2CH2SC(O)CH3)2. In some embodiments, R2is selected from OC(O)CH3, F, and OH. In some embodiments R2is F. In some embodiments, R2is OC(O)CH3. In some embodiments, R2is OH. In some embodiments, R3and R4are each independently selected from OC(O)Rb1and ORa1. In some embodiments, R3and R4are each independently selected from OC(O)CH3 and OH. In some embodiments, R3and R4are each OC(O)CH3. Attorney Docket No.: 00398-0184WO1 In some embodiments, R3is selected from OC(O)Rb1and ORa1. In some embodiments, R3is selected from OC(O)CH3 and OH. In some embodiments, R3is OC(O)CH3. In some embodiments, R3is OH. In some embodiments, R4is selected from OC(O)Rb1and ORa1. In some embodiments, R3is selected from OC(O)CH3 and OH. In some embodiments, R4is OC(O)CH3. In some embodiments, R4is OH. In some embodiments, R5is selected from C1-6alkyl, C2-6alkynyl, and C1-6haloalkyl. In some embodiments, R5is C1-6alkyl. In some embodiments, R5is C2-6alkynyl. In some embodiments, R5is C1-6 haloalkyl. In some embodiments, R5is CH3, CF3, or CCH. In some embodiments, R5is CH3. In some embodiments, R5is CF3. In some embodiments, R5is CCH. In some embodiments, the fucosylation inhibitor is selected from 2F-peracetyl-fucose, A2FF1P, B2FF1P, 6-alkynyl-fucose, 6,6,6-trifluorofucose, Fucostatin II, Fucotrim I, and Fucotrim II. In some embodiments, the fucosylation inhibitor is 2F-peracetyl-fucose, also referred to as “2FF.” 2F-Peracetyl-fucose is a compound having the following structure: , or a pharmaceutically acceptable salt thereof. In some embodiments, the fucosylation inhibitor is A2FF1P, which is the unnatural α‐ anomer of fucose-1‐phosphate. A2FF1P is described in Pijnenborg JFA et al., Chemistry, 2021 Feb 24;27(12):4022-4027. In some embodiments, the fucosylation inhibitor is B2FF1P, which is the endogenous β‐anomer of fucose 1‐phosphate. B2FF1P is described in Pijnenborg et al., Chemistry, 2021 Feb 24;27(12):4022-4027. In some embodiments, the fucosylation inhibitor is 6-alkynyl-fucose, also referred to as “6AF.” 6-alkynyl-fucose is a compound having the structure: Attorney Docket No.: 00398-0184WO1 , or a pharmaceutically acceptable salt thereof. The fucosylation inhibitory properties of 6- alkynyl-fucose are described in, for example, Al-Shareffi et al., Glycobiology, 2013 Feb;23(2):188-98. In some embodiments, the fucosylation inhibitor is 6,6,6-trifluorofucose, also referred to as “Fucostatin I.” 6,6,6-trifluorofucose is a compound having the structure: , or a pharmaceutically acceptable salt thereof. The fucosylation inhibitory properties of ,6,6- trifluorofucose are described in, for example, Scheper et al., Biotechnol Adv. 2023 Oct;67:108184. In some embodiments, the fucosylation inhibitor is a fucose-1-phosphonate analog, which is described in, for example, Scheper et al., Biotechnol Adv. 2023 Oct;67:108184. In some embodiments, the fucosylation inhibitor is Fucostatin II. In some embodiments, the fucosylation inhibitor is a rhamnose 1-phosphate derivatives, which are described in, for example, Scheper et al., Biotechnol Adv. 2023 Oct;67:108184. In some embodiments, the fucosylation inhibitor is Fucotrim I. In some embodiments, the fucosylation inhibitor is Fucotrim II. Attorney Docket No.: 00398-0184WO1 Combination Therapies The methods of the present disclosure can further include the administration of fucosylation inhibitors in combination with other agents for the methods described herein. These agents can be combined with the present compounds in a single dosage form, or the agents can be administered simultaneously or sequentially as separate dosage forms. Routes of administration may vary with combination and embodiment, complimentary to standard therapy. The administration of the fucosylation inhibitor in combination with other agents can include the administration of a 0.0025% to 2.5%, e.g., 0.005%, 0.0075%, 0.01%, 0.05%, 0.075%, 0.1%, 0.25%, 0.5%, 0.75%, 1.0%, 1.25%. 1.5%. 1.75%. 2.0%, 2.25%, or 2.5%, solution or suspension of the fucosylation inhibitor by weight. Suitable agents for use in combination with the fucosylation inhibitors of the present disclosure for the treatment of inflammatory diseases can include, but are not limited to, prednisolone (e.g., prednisolone acetate eye drops), dexamethasone (e.g., dexamethasone eye drops), cyclosporin (e.g., cyclosporin eye drops), fluorometholone (e.g., fluorometholone eye drops), loteprednol (e.g., loteprednol etabonate eye drops), rimexolone (e.g., rimexolone eye drops), doxycycline (e.g., doxycycline eye drops), and diquafosol (e.g., diquafosol eye drops). The administration of prednisolone includes, for example, instilling one to two prednisolone acetate eye drops (having a standard concentration of 0.11 - 2.0%) into the affected eye(s) once or twice daily. The administration of dexamethasone includes, for example, instilling one to two dexamethasone eye drops (having a standard concentration of 0.1%) into the affected eye(s) once or twice daily. The administration of cyclosporin includes, for example, instilling one to two cyclosporin eye drops (having a standard concentration of 0.05 - 0.1%) into the affected eye(s) once or twice daily. The administration of fluorometholone includes, for example, instilling one to two fluorometholone eye drops (having a standard concentration of 0.1% to 0.25%) into the affected eye(s) every four to six hours. The administration of loteprednol includes, for example, instilling one to two loteprednol eye drops (having a standard concentration of 0.2%) into the affected eye(s) once daily. The administration of rimexolone includes, for example, instilling one to two rimexolone eye drops (having a standard concentration of 1%) into the affected eye(s) every four to six hours. The administration of doxycycline includes, for example, instilling one to two doxycycline eye drops (having a standard concentration of 0.025%) into the affected eye(s) every four to six hours. The administration of diquafosol includes, for example, Attorney Docket No.: 00398-0184WO1 instilling one to two diquafosol eye drops (having a standard concentration of 3.0%) into the affected eye(s) daily. In addition, other agents that can be used in combination with the fucosylation inhibitors of the present disclosure for the treatment of inflammatory diseases include but are not limited to corticosteroids (e.g., prednisone, prednisolone, methylprednisolone, and hydrocortisone); disease-modifying antihreumatic drugs (“DMARDs”, e g , immunosuppressive or anti-inflammatory agents); anti-malarial agents (e.g. hydroxychloroquine and chloroquine); immunosuppressive agents (e.g., cyclophosphamide, azathioprine, mycophenolate mofetil, methotrexate); anti-inflammatory agents (e.g., aspirin, NSAIDs (e.g., ibuprofen, naproxen, indomethacin, nabumetone, celecoxib)); anti- hypertensive agents (e.g., calcium channel blockers (e.g., amlodipine, nifedipine) and diuretics (e.g., furosemide)); statins (e.g., atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin); anti-B-cell agents (e.g., anti-CD20 (e.g., rituximab), anti-CD22); anti-B-lymphocyte stimulator agents (“anti-BLyS”, e.g., belimumab, blisibimod); type-1 interferon receptor antagonist (e.g., anifrolumab); T-cell modulators (e.g., rigerimod); abatacept; anticoagulants (e.g., heparin, warfarin); and vitamin D supplements. Additional suitable agents for use in combination with the fucosylation inhibitors of the disclosure for the treatment of inflammatory diseases include but not are not limited to sulfonylureas (e.g., administered .25 to 20 mg once or twice daily; about 0.5, about 1, about 2, about 5, about 10, about 15, or about 20 mg once or twice daily), meglitinides (e.g., administered 0.5 to 2 mg before each meal; about 0.5, about 1, about 1.5, or about 2 mg before each meal), biguanides (e.g., administered 500 to 1000 mg once or twice daily, up to 2550 mg per day), alpha-glucosidase inhibitors (e.g., administered 25 to 100 mg three times daily; about 25, about 50, about 75, or about 100 mg one, two, or three times daily), peroxisome proliferators-activated receptor-gamma (i.e., PPAR-gamma) agonists (e.g., administered 15 to 30 mg daily), insulin and insulin analogues (e.g., dosages vary based on individual needs, ranging from a few units per day to several hundred units per day, administered subcutaneously or via insulin pump), HMG-CoA reductase inhibitors (e.g., administered 10 to 40 mg once daily, with maximum doses up to 80 mg per day), cholesterol- lowering drugs (for example, fibrates that include: fenofibrate, bezafibrate, gemfibrozil, clofibrate and the like [e.g., administered 48 to 145 mg once daily]; bile acid sequestrants which include: cholestyramine, colestipol and the like [administered 4 to 16 grams per day, divided into two or more doses]; and niacin [e.g., administered 250 to 2000 mg per day, Attorney Docket No.: 00398-0184WO1 divided into two or three doses]), anti-platelet agents (for example, aspirin [e.g., administered 75 to 325 mg once daily] and adenosine diphosphate receptor antagonists that include: clopidogrel [e.g., administered 75 mg once daily], ticlopidine and the like), angiotensin- converting enzyme inhibitors (e.g., administered from 2.5 to 10 mg once daily, with maximum doses up to 40 mg per day), angiotensin II receptor antagonists and adiponectin (e.g., administered 25 to 50 mg once daily, with maximum doses up to 150 mg per day). EXAMPLES The following examples include the preparation and evaluation of the pharmaceutical formulations of the disclosure. General Experimental Methods Human Corneal Tissue Postmortem corneoscleral tissues from humans with no ocular disease at time of death were obtained from Lions VisionGift (Portland, OR, USA) or Saving Sight (Kansas City, Mo). Mean donor age was 60.39 ± 7.56 years. The average time from death to preservation of corneo-scleral tissue was 16.67 hours ± 0.33 hours. Standard serologies for infectious agents were negative for all donors. Growth-Arrested 3T3-J2 Cells 3T3-J2 mouse fibroblasts (Kerafast, New York, USA) were cultured in Dulbecco’s modified Eagle’s medium (DMEM) (#10569044, ThermoFisher Scientific) with 10% bovine calf serum (BCS; SH30072.03; Hyclone, Pittsburgh, USA) and 1% penicillin / streptomycin (#115140-122; Thermo Fisher Scientific) in a humidified incubator with 5% CO2. Fibroblasts were mitotically inactivated by incubation with 4 µg / mL mitomycin-C (M4287, Sigma- Aldrich) for 2 hours at 37°C in a humidified incubator with 5% CO2. Cells were then rinsed five times with Dulbecco's-modified phosphate-buffered saline (DPBS) lacking calcium and magnesium (Thermo Fisher Scientific), detached with TrypLE™ Express (Thermo Fisher Scientific) and frozen in DMEM supplemented with 20% BCS and 10% dimethylsulfoxide (DMSO; Sigma-Aldrich) for 24 hours before cryopreservation in liquid nitrogen. Cell Culture of limbal stem cells For the culture of human limbal epithelial cells, growth-arrested 3T3-J2 fibroblasts were suspended in DMEM GlutaMAX™ with 10% fetal bovine serum and plated at a density Attorney Docket No.: 00398-0184WO1 of 4.6 × 104cells / cm2in a 100-mm tissue culture dish (Corning, Glendale, AZ, USA). On the following day, limbal epithelial cells were harvested from corneoscleral tissues and seeded in 100-mm tissue culture dishes containing growth-arrested 3T3-J2 fibroblasts. The medium was changed on the following day and every other day thereafter. After 7 days, the 3T3-J2 feeder cells were detached using Versene (Thermo Fisher Scientific) for approximately 1 min, followed by a wash in Dulbecco’s modified phosphate-buffered saline, and a 10-min incubation with TrypLE Express to detach the epithelial cells. Limbal stem cell were pelleted by centrifugation and frozen in DMEM GlutaMAX™ supplemented with 20% fetal bovine serum and 10% DMSO. Statistical Analysis All experiments were performed 3 individual times using three to four biological replicates. Statistical analysis was performed using Prism software version 9 (GraphPad Software, San Diego, CA, USA). Student t test was used unless otherwise denoted. P > 0.05: Not significant (no asterisks), P ≤ 0.05: *, P ≤ 0.01: **, P ≤ 0.001: ***. Example 1 - qPCR Fucosylation Mediators Following Inflammatory Stress To assess if TNF-α, a key inflammatory mediator in LSCD pathology, promotes the expression of fucose biosynthesis genes, limbal stem cells were treated with 0 ng / ml, 100 ng / ml or 1,000 ng / ml of TNF-α and TSTA3, and GMDS expression levels were assessed by quantitative real-time PCR. The SsoAdvanced™ Universal SYBR® Green Supermix™ (Bio- Rad) in a Mastercycler™ RealPlex™ 2 (Eppendorf). Primers for GMDS (OriGene : NM_002046), TSTA3 (IDT : HS.pt.58.4263683), and GAPDH (Biorad: cat. no. qHsaCED0038674), were used for the detection of GMDS, TSTA3, and GAPDH transcripts. The following parameters were used: 5 min at 95°C, followed by 40 cycles of 5 sec at 95°C and 30 sec at 60°C. All samples were normalized using GAPDH housekeeping gene expression. The comparative ΔΔCT method was used for relative quantitation of the number of transcripts. This figure indicates that TNF-α stimulation induces robust expression of fucosylation genes in limbal epithelial stem cells. (FIGs. 1A – 1B). The upregulation of these fucose biosynthesis genes by TNF-α is pronounced, ranging from 10 to 80-fold higher levels of GMDS and TSTA3 in TNF-α stimulated cells compared to untreated controls. Attorney Docket No.: 00398-0184WO1 Example 2 - Immunofluorescence Microscopy To determine the extent of fucose present on the cell surface and confirm efficacy of fucosylation inhibition, primary limbal stem cells treated with 2F-Peracetyl-Fucose (2FF) for 72 hours were labeled with a fluorescent fucose binding lectin (AAL-FITC). Limbal stem cells in 24 well tissue culture plates were incubated with 1 µg / mL of fluorescein-conjugated Aleuria Aurantia Lectin (AAL; Vector Laboratories, Burlingame, CA, USA) for 2 hours, then washed with DPBS 3 times. A BioTek Lionheart FX automated microscope was used to visualize wells with FITC detected at 519 nm. FIG. 2A is a microscopic image of the limbal stem cell culture, tagged with fluorescein, in the presence of DMSO (control) and in the absence of the fucosylation inhibitor 2FF. In the absence of a fucosylation inhibitor, the fluorescent tag binds to fucose, and the image glows (white). In the presence of a fucosylation inhibitor, there is little fucose present for the fluorescent tag to bind to, resulting in a nearly black image. Thus, as shown in FIG. 2B, 2FF is highly effective in inhibiting fucosylation on limbal stem cells in culture. Thus, 2FF is a potent fucosylation inhibitor that can be used in the claimed methods. Example 3 - Cell Death Assay Limbal stem cells were subjected to a cell death assay to determine the extent to which the inhibition of fucosylation promotes the survival of limbal cells. Limbal stem cells were cultured as described above with the adaptation that 12 hours after plating onto 3T3, feeder layer cells were exposed to 100 µM 2F-Peracetyl- Fucose (2FF; Sigma-Aldrich) or equal volume vehicle control (DMSO), this which was refreshed every 24 hours for 72 hours prior to start of the cell death assay. 3T3 feeder cells were removed by veresene treatment and limbal stem cells were detached using TrypLE Express as described above. Harvested limbal stem cells were replated onto 384 well optical bottom plates (Thermofischer) at a density of 1 × 104 cm2in RPMI containing 100 µM 2FF or equal volume DMSO, either alone (controls) or in conjunction with recombinant human tumor necrosis factor alpha (rhTNF-α, 100ng / ml, Peprotech) + 5Z-7-Oxozeaenol (5z7, 125 nM, SigmaAldrich). Live imaging was performed using the BioTek Lionheart FX automated microscope with built-in environmental control maintained at 37 °C, 5% CO2for the duration of the assay. Cells were imaged at 30-min intervals for 28 hours at ×4 magnification to capture ~5000 cells / field of view. Propidium iodide (PI) incorporation was detected at 617 nm, and Attorney Docket No.: 00398-0184WO1 PI+ nuclei were counted. Hoescht was detected at 461 nm and Hoescht+ nuclei were counted. For every time point, PI+ nuclei / Hoescht+ nuclei = percent cell death. FIG. 3A depicts the cell death curve over 28-hour period post-exposure to a high dose of TNF-α+5z7. As can be seen in FIG. 3A, in the absence of TNF-α, the percentage of cell death remains low, around 20% for both the DMSO (control) and 2FF experiments. However, in the presence of TNFα, which promotes cell death, the percentage of cell death increases to greater than 60% cell death for the DMSO control group. However, in the presence of the fucosylation inhibitor 2FF, the percentage of cell death is reduced greatly, even in the presence of TNF-α. FIGs. 3B and 3C depict representative images from hour 17 with nuclei in dark gray and dead cells in light gray. Propidium Iodide (PI - white), is used to mark dead cells, while Hoescht (grey), is a nuclear stain. FIG. 3B-2 on the right indicates that 2FF treated primary limbal cells have enhanced survival (far fewer dead, white, cells) when challenged with the inflammatory molecule TNF-α+5z7. This result supports the use of fucosylation inhibitors in the promotion of limbal cells, and therefore in the treatment of ocular diseases and disorders characterized by dysfunction of limbal stem cells. Example 4 - qPCR Array for Apoptosis Genes To determine what transcriptional changes may underlie enhanced viability of 2FF pretreated cells in the cell death assay, a qPCR array was performed. The relative mRNA expression of 84 genes regulating cell death and survival were analyzed using the RT2 Profiler PCR Human Apoptosis Array (Qiagen : Cat. No.: 330231) according to the manufacturer's instructions. Limbal stem cells were cultured 3 days with 2FF or without (DMSO), then treated with TNFα+5Z7 for 0 hours (unstimulated), 4 hours or 24 hours. Samples were normalized using the mean of several housekeeping genes. The 2-ΔΔCTmethod was used for relative quantitation of the number of transcripts normalized to untreated control from same group. The array was repeated 3 times from 3 limbal donors and the mRNA was isolated independently. FIGS. 4A-4C depict qPCR array data showing relative expression of 84 cell death and / or cell survival related genes in limbal stem cells cultured for 3 days with 2FF or without (DMSO) then treated with TNF-α+5Z7 for 0 hours (unstimulated), 4 hours, and 24 hours. Attorney Docket No.: 00398-0184WO1 The pro-survival genes BCL2, BAG3, and BIRC3 were found to be significantly higher in the 2FF group at 24 hours post-exposure (FIG. 4C). Example 5 - Population Doubling Assay Limbal stem cells were subjected to a cell death assay to determine the extent to which the inhibition of fucosylation promotes the proliferation of limbal cells. Limbal stem cells (100 cells / cm2) from 3 donors were plated onto 3T3-J2 feeder layers in a 6-well tissue culture plate and treated with 10 ng / ml rhTNF-α (Peprotech) and 1 nM 5Z-7-Oxozeaenol (SigmaAldrich). Cells from each donor were treated with 100 µM 2F-Peracetyl-Fucose (2FF; Sigma-Aldrich) or equal volume DMSO vehicle control. Once each well reached 85% confluency cells were counted and replated at 100 cells / cm2. Population doubling values calculated as log2(number of cells harvested / number of cells seeded). The graphs in FIGs. 5A to 5C show the cumulative population doubling of limbal stem cells cultured with low-dose TNF-α+5Z7 either in the presence or absence of 2FF in three different donors. The graphs demonstrate that 2FF treatment results in enhanced cumulative population doublings (e.g., around 10-15 cumulative population doublings) in the presence of a subacute dose of TNF-α+5Z7, compared to the absence of 2FF, in which the cumulative population doublings remains below 10. This result demonstrates that the presence of the fucosylation inhibitor 2FF promotes limbal stem cell growth. The graphs in FIGs. 6A to 6E shows that 2FF reduces population doubling time across five passages of limbal stem cells continuously exposed to low doses of TNF-α+527 and either a DMSO vehicle (control) or 2FF. The figures show that the population doubling time of the limbal stem cell culture is greatly reduced in the presence of the fucosylation inhibitor 2FF, meaning that the presence of 2FF greatly promotes limbal stem cell culture growth. These results support the use of fucosylation inhibitors in the promotion of limbal epithelial stem cell viability and proliferative capacity, and therefore in the treatment of ocular diseases and disorders characterized by dysfunction of limbal stem cells. Example 6 - Molecular Modeling Structural modeling of TNF receptor complex was conducted to predict N- glycosylation sites of the complex. Attorney Docket No.: 00398-0184WO1 Structural modeling was performed using PyMOL (Molecular Graphics System, version 2.0, Schrödinger) of the TNFR1-TNF complex retrieved from the Protein DataBase. TNFR1 is depicted as a gray ribbon or space filling model, with dark gray spheres labeling N-glycosylation sites predicted by NNetGlyc V 1.0 ( See, online at cbs.dtu.dk / services / NetNGlyc / ). TNF is shown as a light gray space-filling model. TNFR2 (black ribbon diagram, gray spheres labeling predicted glycosites) was superimposed onto the structure of TNFR1 using PyMOL. FIG. 7A shows the structure of TNFR1 (grey ribbon structure) with labeled predicted N-glycosylation sites (dark gray spheres) and TNF (gray space filled model). FIG. 7B shows that one N-glycosylation site (N145) is in close spatial proximity to the TNF- TNFR1 binding site, potentially indicating a glycan may regulate this interaction. FIG. 7C shows overlaid structures of TNFR1 and TNFR2 with predicted N glycosylation sites highlighted in dark gray and lighter gray spheres respectively, and that 1 N-glycosite is conserved between receptors. The results indicate that fucose containing glycans regulate the TNF-TNFR1 binding site, and therefore mediate inflammatory and cell death processes. Example 7 - Alkaline Burn Model A study is conducted to investigate the effects of a fucosylation inhibitor (e.g., 2FF) in an in vivo model to evaluate its impact on LSC survival and disease outcomes. To do so, an alkaline corneal burn model is used, as alkaline burns are a leading cause of LSCD in humans and the most widely established animal model for studying this condition. Experimental Design To investigate the role of fucosylation inhibition in LSC survival and corneal repair, wild-type (WT) C57B6 mice are treated with a fucosylation inhibitor (e.g., 2FF) (100 µM eye drops, every 24 hours) or vehicle control (DMSO) for 10 days prior to injury and maintained on the same regimen throughout the post-injury period. Mice then undergo an NaOH corneal burn protocol, and the following experiments are performed to assess LSC function and corneal regeneration. Attorney Docket No.: 00398-0184WO1 Label Retention Assays To assess LSC proliferation and self-renewal, mice receive intraperitoneal injections of 5-bromo-2’-deoxyuridine (BrdU) (200 µg / g body weight) two hours before corneal injury. Corneal wounds are then induced using 1M NaOH, and tissue are harvested at 1, 2, 4, 7, 14, and 21 days post-wound. Tissue sections are processed and imaged, and the number and spatial distribution of BrdU-positive cells within the limbus and regenerated corneal epithelium are quantified. RNAScope for Stem Cell and Cell Death Markers To further characterize the impact of the fucosylation inhibitor (e.g., 2FF) on LSC survival, transcript expression of key stem cell and cell death markers is analyzed using RNAScope in situ hybridization. Corneal tissue is sectioned and hybridized with probes for LSC markers, including Abcb5, Ck15, Abcg2, and ΔNp63, as well as apoptosis-related genes. Cell death markers include Caspases 3, 7, 8, and 9, along with pro-apoptotic genes Bak, Bax, and Bim. Survival-promoting genes such as BIRC family members, Bcl2, Bcl10, Bclxl, and MAPKs (Erk, Jnk) are also assessed. Corneal Regeneration and Wound Healing Analysis Corneal regeneration is assessed through corneal opacity scoring and wound healing / re-epithelialization rate at 6, 12, 24, 48, 72, and 96 hours post-injury. Corneal Opacity: Opacity is graded using a dissection microscope based on the following scale: 0 – No opacity; 1 – Less than one-third of the cornea clouded; 2 – Less than two-thirds clouded; 3 – More than two-thirds clouded; 4 – Entire cornea clouded, obscuring pupil margins. Wound Healing Rate: The degree of re-epithelialization is evaluated using fluorescein staining and ImageJ analysis. Wounds are classified as open (not fully re- epithelialized) or closed (fully re-epithelialized), and the average time to full closure is compared between the fucosylation inhibitor (e.g., 2FF)-treated and vehicle-treated mice. Anticipated Results It is expected that 2FF-treated mice exhibit enhanced LSC survival, evidenced by increased retention of BrdU-positive cells and upregulation of stem cell markers. In addition, it is expected that fewer apoptotic cells and higher expression of survival-promoting genes in the limbal basal epithelium following injury will be observed. Functionally, it is expected that Attorney Docket No.: 00398-0184WO1 fucosylation inhibitor (e.g., 2FF) treatment will accelerate corneal wound healing and reduces corneal opacity, supporting the premise that fucosylation inhibition mitigates inflammation- induced LSC loss. Together, these experiments provide a comprehensive evaluation of whether the fucosylation inhibitor (e.g., 2FF) preserves LSC function, enhances corneal regeneration, and mitigates the progression of LSCD. Example 8 - Ex Vivo Human Organ Culture Model Rationale and Approach A study is conducted to investigate the effects of a fucosylation inhibitor (e.g., 2FF) in an ex vivo human corneal organ culture model to evaluate its impact on LSC survival, proliferation, and epithelial regeneration under inflammatory conditions. A human donor’s corneas maintained in an air-liquid interface organ culture system are used to assess the effect of the fucosylation inhibitor (e.g., 2FF) on LSC viability, stem cell marker expression, and corneal epithelial repair following inflammatory insult. Experimental Design To investigate the role of fucosylation inhibition in LSC survival and corneal regeneration, human donor corneas are obtained from an eye bank and maintained in an air- liquid interface organ culture system. The corneas are divided into the following experimental groups: 1. Control (normal media, DMSO vehicle) 2. Inflammation only (TNF-α + IL-1β, DMSO vehicle) 3. Inflammation + 2FF (TNF-α + IL-1β, 2FF) Corneas in the inflammation groups are treated with TNF-α (100 ng / mL) + IL-1β (50 ng / mL) for the 72 hours to mimic an inflammatory ocular surface environment, such as that following a wound. The fucosylation inhibitor (e.g., 2FF)-treated group receives 100 µM fucosylation inhibitor (e.g., 2FF) in culture media and every 24 hours. Immunohistochemistry for Stem Cell Viability To further characterize the impact of the fucosylation inhibitor (e.g., 2FF) on LSC survival, immunohistochemistry (IHC) is performed to assess stem cell markers and apoptotic proteins in limbal tissue sections. Stem cell markers include ABCB5, CK15, ABCG2, and ΔNp63, while apoptotic markers such as CASPASE(s) 3, 7, 8, and 9, BAK, BAX, and BIM Attorney Docket No.: 00398-0184WO1 are evaluated to determine whether the fucosylation inhibitor (e.g., 2FF) reduces inflammation-induced LSC loss. Proliferation is assessed using Ki67 immunohistochemistry (IHC), a marker of actively cycling cells. Expression of survival-promoting proteins such as BIRC family members, BCL2, BCL10, BCLXL, and MAPKs (ERK, JNK). Additionally, a TUNEL assay is performed to quantify apoptotic cell death within the limbal sections. Corneal Regeneration and Barrier Function To assess corneal epithelial integrity, a FITC-dextran permeability assay is performed to evaluate barrier function. Increased permeability indicates epithelial damage, which would suggest impaired LSC function. Corneal epithelial regeneration is also assessed using a standardized 8-mm epithelial debridement model, where re-epithelialization is tracked at 6, 12, 24, 48, and 72 hours post-wound using fluorescein staining and ImageJ analysis. The rate of epithelial closure is compared between the fucosylation inhibitor (e.g., 2FF)-treated and vehicle-treated corneas to determine whether the fucosylation inhibitor enhances regenerative capacity. Anticipated Results It is expected that the fucosylation inhibitor (e.g., 2FF)-treated corneas exhibit enhanced LSC survival, as indicated by increased stem cell marker levels and Ki67 positivity, higher expression of survival-promoting proteins, and fewer apoptotic cells in the limbal basal epithelium following inflammatory insult. Functionally, it is expected that the fucosylation inhibitor (e.g., 2FF) maintains corneal barrier integrity, reduces epithelial permeability, and accelerates wound healing, supporting the premise that fucosylation inhibition mitigates inflammation-induced LSC loss and improves corneal regeneration. Together, these experiments provide a clinically relevant ex vivo model for assessing the fucosylation inhibitor’s (e.g., 2FF) therapeutic potential in preserving LSC function and promoting corneal repair under inflammatory conditions. OTHER EMBODIMENTS While various embodiments of the present disclosure have been shown and described herein, such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will occur to those skilled in the art without departing from the inventions recited in the following claims. It should be understood that various alternatives to Attorney Docket No.: 00398-0184WO1 the embodiments of the disclosure can be employed in practice. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of the claims and their equivalents be covered thereby.

Claims

Attorney Docket No.: 00398-0184WO1 WHAT IS CLAIMED IS:

1. A fucosylation inhibitor for use in preserving the viability of limbal stem cells in a subject in need thereof.

2. A fucosylation inhibitor for use in treating, inhibiting, or preventing limbal stem cell deficiency in a subject in need thereof.

3. The fucosylation inhibitor of claim 1 or 2, wherein the fucosylation inhibitor is a compound having Formula (I):(I), or a pharmaceutically acceptable salt thereof, wherein: R1and R2are each independently selected from halo, ORa, SRa, C(O)Rb, C(O)NRcRd,and OP(O)(ORa)2; R3and R4are each independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6haloalkyl, halo, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, C(=NRe1)Rb1, C(=NORa1)Rb1, C(=NRe1)NRc1Rd1, NRc1C(=NRe1)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, S(O)2NRc1Rd1, P(O)(NH2)ORa1, and OP(O)(ORa1)2; wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with a substituent independently selected from CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, C(=NRe1)Rb1, C(=NORa1)Rb1, C(=NRe1)NRc1Rd1, NRc1C(=NRe1)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, S(O)2NRc1Rd1, P(O)(NH2)ORa1, and OP(O)(ORa1)2; R5is selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C1-6haloalkyl;Attorney Docket No.: 00398-0184WO1 each Ra, Rc, Rd, Ra1, Rc1, and Rd1is independently selected from H, C1-6alkyl, C2-6alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg; each Rband Rb1is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg; each Reand Re1is independently selected from H, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkylthio, C1-6alkylsulfonyl, C1-6alkylcarbonyl, C1-6alkylaminosulfonyl, carbamyl, C1-6alkylcarbamyl, di(C1-6 alkyl)carbamyl, aminosulfonyl, C1-6 alkylaminosulfonyl and di(C1-6 alkyl)aminosulfonyl; and each Rgis independently selected from OH, NO2, CN, SC(O)C1-6alkyl, halo, C1-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-3 alkoxy-C1-3 alkyl, C1-3alkoxy-C1-3alkoxy, HO-C1-3alkoxy, HO-C1-3alkyl, cyano-C1-3alkyl, H2N-C1-3alkyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, thio, C1-6alkylthio, C1-6alkylsulfinyl, C1-6alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6alkylaminosulfonyl, di(C1-6alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino.

4. The fucosylation inhibitor of claim 3, wherein R1and R2are each independently selected from OC(O)Rb, halo, ORa, and OP(O)(ORa)2.

5. The fucosylation inhibitor of claim 3, wherein R1and R2are each independently selected from OC(O)CH3, F, OH, and OP(O)(OCH2CH2SC(O)CH3)2.

6. The fucosylation inhibitor of claim 3, wherein R1is OC(O)CH3, and R2is F.

7. The fucosylation inhibitor of any one of claims 3-6, wherein R3and R4are each independently selected from OC(O)Rb1and ORa1.

8. The fucosylation inhibitor of any one of claims 3-6, wherein R3and R4are each independently selected from OC(O)CH3 and OH.

9. The fucosylation inhibitor of any one of claims 3-6, wherein R3and R4are each OC(O)CH3.Attorney Docket No.: 00398-0184WO1 10. The fucosylation inhibitor of any one of claims 3-9, wherein R5is selected from C1-6alkyl, C2-6 alkynyl, and C1-6 haloalkyl.

11. The fucosylation inhibitor of any one of claims 3-9, wherein R5is CH3, CF3, or CCH.

12. The fucosylation inhibitor of any one of claims 3-9, wherein R5is CH3.

13. The fucosylation inhibitor of claim 1 or 2, wherein the fucosylation inhibitor is any one or more of 2F-Peracetyl-Fucose, A2FF1P, B2FF1P, 6-alkynyl-fucose, 6,6,6- trifluorofucose, Fucostatin II, Fucotrim I, or Fucotrim II.

14. The fucosylation inhibitor of claim 1 or 2, wherein the fucosylation inhibitor is 2F- peracetyl-Fucose.

15. The fucosylation inhibitor of any one of claims 1-14, wherein the subject has an ocular disorder.

16. The fucosylation inhibitor of claim 15, wherein the ocular disorder is an autoimmune disease, a congenital disease, an infectious disease, or a traumatic insult.

17. The fucosylation inhibitor of claim 16, wherein the ocular disorder is an autoimmune disease.

18. The fucosylation inhibitor of claim 17, wherein the autoimmune disease is Stevens- Johnson syndrome, Sjögren's syndrome, or ocular cicatricial mucous membrane pemphigoid.

19. The fucosylation inhibitor of claim 16, wherein the ocular disorder is a congenital disease.

20. The fucosylation inhibitor of claim 19, wherein the congenital disease is dominantly inherited keratitis, ectodermal dysplasia, or aniridia.

21. The fucosylation inhibitor of claim 16, wherein the ocular disorder is an infectious disease.

22. The fucosylation inhibitor of claim 21, wherein the infectious disease is herpes simplex keratitis or trachoma.Attorney Docket No.: 00398-0184WO1 23. The fucosylation inhibitor of claim 16, wherein the ocular disorder is a traumatic insult.

24. The fucosylation inhibitor of claim 23, wherein the traumatic insult is a chemical injury, a thermal injury, or a physical injury.

25. The fucosylation inhibitor of any one of claims 1-24, wherein the fucosylation inhibitor is administered topically.

26. The fucosylation inhibitor of claim 25, wherein the topical administration comprises instilling an aliquot of a solution or suspension of the fucosylation inhibitor into the afflicted eye or eyes of the subject.

27. The fucosylation inhibitor of claim 26, wherein the aliquot is 1-5 drops of the solution or suspension of the fucosylation inhibitor.

28. The fucosylation inhibitor of claim 26, wherein the aliquot is one drop of the solution or suspension of the fucosylation inhibitor.

29. The fucosylation inhibitor of claim 26, wherein the solution or suspension is an aqueous solution or suspension.

30. The fucosylation inhibitor of claim 26, wherein the solution is a non-aqueous solution.

31. The fucosylation inhibitor of any one of claims 1-30, wherein the administering comprises intravitreally injecting a solution of the fucosylation inhibitor into the eye of the subject.

32. The fucosylation inhibitor of claim 31, wherein the solution is an aqueous solution.

33. A fucosylation inhibitor for use in the treatment of an inflammatory ocular disorder in a subject in need thereof, wherein the fucosylation inhibitor is any one or more of 2F- Peracetyl-Fucose, A2FF1P, B2FF1P, 6-alkynyl-fucose, 6,6,6-trifluorofucose, Fucostatin II, Fucotrim I, and Fucotrim II.

34. The fucosylation inhibitor of claim 33, wherein the fucosylation inhibitor is 2F- peracetyl-Fucose.Attorney Docket No.: 00398-0184WO1 35. The fucosylation inhibitor of claim 33 or 34, wherein the ocular disorder is an autoimmune disease, a congenital disease, an infectious disease, or a traumatic insult.

36. The fucosylation inhibitor of claim 35, wherein the ocular disorder is an autoimmune disease.

37. The fucosylation inhibitor of claim 36, wherein the autoimmune disease is Stevens- Johnson syndrome, Sjögren's syndrome, or ocular cicatricial mucous membrane pemphigoid.

38. The fucosylation inhibitor of claim 35, wherein the ocular disorder is a congenital disease.

39. The fucosylation inhibitor of claim 38, wherein the congenital disease is dominantly inherited keratitis, ectodermal dysplasia, or aniridia.

40. The fucosylation inhibitor of claim 35, wherein the ocular disorder is an infectious disease.

41. The fucosylation inhibitor of claim 40, wherein the infectious disease is herpes simplex keratitis or trachoma.

42. The fucosylation inhibitor of claim 35, wherein the ocular disorder is a traumatic insult.

43. The fucosylation inhibitor of claim 42, wherein the traumatic insult is a chemical injury, a thermal injury, or a physical injury.

44. The fucosylation inhibitor of any one of claims 33-43, wherein the fucosylation inhibitor is administered topically.

45. The fucosylation inhibitor of claim 44, wherein the topical administration comprises instilling an aliquot of a solution or suspension of the fucosylation inhibitor into the afflicted eye or eyes of the subject.

46. The fucosylation inhibitor of claim 45, wherein the aliquot is 1-5 drops of the solution or suspension of the fucosylation inhibitor.

47. The fucosylation inhibitor of claim 45, wherein the aliquot is one drop of the solution or suspension of the fucosylation inhibitor.Attorney Docket No.: 00398-0184WO1 48. The fucosylation inhibitor of claim 45, wherein the solution or suspension is an aqueous solution or suspension.

49. The fucosylation inhibitor of claim 45, wherein the solution is a non-aqueous solution.

50. The fucosylation inhibitor of any one of claims 33-49, wherein the administering comprises intravitreally injecting a solution of the fucosylation inhibitor into the eye of the subject.

51. The fucosylation inhibitor of claim 50, wherein the solution is an aqueous solution.

52. A method of treating an inflammatory ocular disorder in a subject in need thereof, the method comprising administering to an afflicted eye of the subject a therapeutically effective amount of a fucosylation inhibitor, wherein the fucosylation inhibitor is any one or more of 2F-Peracetyl-Fucose, A2FF1P, B2FF1P, 6-alkynyl-fucose, 6,6,6-trifluorofucose, Fucostatin II, Fucotrim I, or Fucotrim II.

53. The method of claim 52, wherein the fucosylation inhibitor is 2F-peracetyl-Fucose.

54. The method of claim 52 or 53, wherein the therapeutically effective amount comprises a concentration of the fucosylation inhibitor effective to reduce death of limbal stem cells in the afflicted eye.

55. A method of enhancing the viability of limbal stem cells in vitro, the method comprising adding to a culture of limbal stem cells a fucosylation inhibitor in an amount effective to reduce death of the limbal stem cells.

56. A method of treating a limbal stem cell deficiency in a subject in need thereof, the method comprising storing or culturing limbal stem cells in the presence of a fucosylation inhibitor to provide cultured limbal stem cells, and transplanting the cultured limbal stem cells to the eye of the subject.

57. The method of claim 56, wherein the transplanting comprises using a transplantation technique selected from Conjunctival Limbal Autograft (CLAU), Cultivated Limbal Epithelial Transplantation (CLET), Living-Related Conjunctival Limbal Allograft (LR- CLAL), or Keratolimbal Allograft (KLAL).Attorney Docket No.: 00398-0184WO1 58. The method of claim 56 or 57, wherein the limbal stem cells are stored or cultured ex vivo.

59. The method of any one of claims 56-58, wherein the limbal stem cells are cultured in a base-media composition.

60. The method of claim 59, wherein the base-media composition comprises fetal bovine serum (FBS).

61. The method of claim 60, wherein the base-media composition comprises about 5% to about 25% FBS by weight.

62. The method of any one of claims 59-61, wherein the base-media composition further comprises hydrocortisone.

63. The method of claim 62, wherein the base-media composition comprises about 0.1 μg / mL to about 2 μg / mL hydrocortisone.

64. The method of any one of claims 59-63, wherein the base-media composition further comprises insulin.

65. The method of claim 64, wherein the base-media composition comprises about 1 μg / mL to about 15 μg / mL insulin.

66. The method of any one of claims 59-65, wherein the base-media composition further comprises triiodothryonine.

67. The method of claim 66, wherein the base-media composition comprises about 1 ng / mL to about 10 ng / mL triiodothryonine.

68. The method of any one of claims 59-67, wherein the base-media composition further comprises adenine.

69. The method of claim 68, wherein the base-media composition comprises about 1 μg / mL to about 100 μg / mL adenine.

70. The method of any one of claims 59-67, wherein the base-media composition further comprises epidermal growth factor.Attorney Docket No.: 00398-0184WO1 71. The method of claim 70, wherein the base-media composition comprises about 1 μg / mL to about 100 μg / mL epidermal growth factor.

72. A method for reducing limbal stem cell death, the method comprising contacting limbal stem cells with a fucosylation inhibitor.

73. The method of claim 72, wherein the contacting occurs ex vivo.

74. The method of claim 73, wherein the contacting comprises storing and culturing limbal stem cells in the presence of a fucosylation inhibitor.

75. The method of any one of claims 52-74, wherein the fucosylation inhibitor is a compound having Formula (I):(I), or a pharmaceutically acceptable salt thereof, wherein: R1and R2are each independently selected from halo, ORa, SRa, C(O)Rb, C(O)NRcRd,and OP(O)(ORa)2; R3and R4are each independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6 haloalkyl, halo, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, C(=NRe1)Rb1, C(=NORa1)Rb1, C(=NRe1)NRc1Rd1, NRc1C(=NRe1)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, S(O)2NRc1Rd1, P(O)(NH2)ORa1, and OP(O)(ORa1)2; wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with a substituent independently selected from CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, C(=NRe1)Rb1, C(=NORa1)Rb1, C(=NRe1)NRc1Rd1,Attorney Docket No.: 00398-0184WO1 NRc1C(=NRe1)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, S(O)2NRc1Rd1, P(O)(NH2)ORa1, and OP(O)(ORa1)2; R5is selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C1-6haloalkyl; each Ra, Rc, Rd, Ra1, Rc1, and Rd1is independently selected from H, C1-6alkyl, C2-6alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg; each Rband Rb1is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C1-6haloalkyl; wherein said C1-6alkyl, C2-6alkenyl and C2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg; each Reand Re1is independently selected from H, CN, C1-6alkyl, C1-6haloalkyl, C1-6alkylthio, C1-6alkylsulfonyl, C1-6alkylcarbonyl, C1-6alkylaminosulfonyl, carbamyl, C1-6alkylcarbamyl, di(C1-6 alkyl)carbamyl, aminosulfonyl, C1-6 alkylaminosulfonyl and di(C1-6 alkyl)aminosulfonyl; and each Rgis independently selected from OH, NO2, CN, SC(O)C1-6alkyl, halo, C1-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-3 alkoxy-C1-3 alkyl, C1-3 alkoxy-C1-3 alkoxy, HO-C1-3 alkoxy, HO-C1-3 alkyl, cyano-C1-3 alkyl, H2N-C1-3 alkyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, thio, C1-6alkylthio, C1-6alkylsulfinyl, C1-6alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6alkylaminosulfonyl, di(C1-6alkyl)aminosulfonyl, aminosulfonylamino, C1-6alkylaminosulfonylamino, di(C1-6alkyl)aminosulfonylamino, aminocarbonylamino, C1-6alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino.

76. The method of claim 75, wherein R1and R2are each independently selected from OC(O)Rb, halo, ORa, and OP(O)(ORa)2.

77. The method of claim 75, wherein R1and R2are each independently selected from OC(O)CH3, F, OH, and OP(O)(OCH2CH2SC(O)CH3)2.

78. The method of claim 75, wherein R1is OC(O)CH3, and R2is F.

79. The method of any one of claims 75-78, wherein R3and R4are each independently selected from OC(O)Rb1and ORa1.

80. The method of any one of claims 75-78, wherein R3and R4are each independently selected from OC(O)CH3and OH.Attorney Docket No.: 00398-0184WO1 81. The method of any one of claims 75-78, wherein R3and R4are each OC(O)CH3.

82. The method of any one of claims 75-81, wherein R5is selected from C1-6 alkyl, C2-6 alkynyl, and C1-6haloalkyl.

83. The method of any one of claims 75-81, wherein R5is CH3, CF3, or CCH.

84. The method of any one of claims 75-81, wherein R5is CH3.

85. The method of any one of claims 52-74, wherein the fucosylation inhibitor is any one or more of 2F-Peracetyl-Fucose, A2FF1P, B2FF1P, 6-alkynyl-fucose, 6,6,6-trifluorofucose, Fucostatin II, Fucotrim I, and Fucotrim II.

86. The method of any one of claims 52-74, wherein the fucosylation inhibitor is 2F- peracetyl-Fucose.

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