Compositions for the prevention or treatment of macular degeneration, containing GV1001

Abstract

The present invention relates to a pharmaceutical composition for the prevention or treatment of macular degeneration, and more particularly to a pharmaceutical composition for the prevention or treatment of macular degeneration that contains a peptide having the amino acid sequence of SEQ ID NO: 1, exhibits an effect of reducing retinal degeneration, is safe for the body, and has few side effects, including abnormal reactions.

Description

Technical Field

[0001] The present invention relates to a composition for preventing or treating macular degeneration containing GV1001.

Background Art

[0002] Age-related macular degeneration (AMD) is an eye disease in which the function of the macula, the central part of the retina where images are focused, is impaired, and vision is gradually lost from the center of the visual field, leading to blindness. Age-related macular degeneration is divided into dry AMD, which is caused by the accumulation of cellular metabolic waste products such as drusen and amyloid beta (Aβ), and wet AMD, in which new blood vessels are generated and vision is lost due to bleeding and fluid leakage.

[0003] Dry AMD is continuously exposed to stress situations such as oxidative stress, causing the death and degeneration of retinal cells. The death and degeneration of retinal cells cause the dense retinal layer to loosen, and new blood vessels are generated by cytokines and growth factors secreted, progressing to wet AMD. Therefore, treatment at the dry AMD stage is extremely important.

[0004] In the case of wet AMD, it is known that newly generated blood vessels produced by vascular endothelial growth factor (VEGF) are the direct cause, and currently, drugs targeting VEGF such as Eylea (registered trademark) are used as therapeutic agents.

[0005] Unlike wet macular degeneration, for which many treatments are commercially available, there is currently only one FDA-approved drug for dry macular degeneration. Therefore, there is an urgent need to develop a treatment for dry macular degeneration that can regulate the early progression of age-related macular degeneration.

[0006] Therefore, after diligent research, the inventors discovered that age-related macular degeneration can be treated by reducing reactive oxygen species (ROS) and decreasing the degeneration of retinal pigment epithelial cells (RPE cells), thus completing the present invention. [Overview of the Initiative] [Problems that the invention aims to solve]

[0007] The present invention aims to provide a pharmaceutical composition for the prevention or treatment of macular degeneration.

[0008] The present invention aims to provide a pharmaceutical composition for the prevention or treatment of age-related macular degeneration.

[0009] The present invention aims to provide a kit for the prevention or treatment of macular degeneration.

[0010] The present invention aims to provide a health functional food for the prevention or improvement of macular degeneration.

[0011] The present invention aims to provide a health functional food for preventing or improving age-related macular degeneration. [Means for solving the problem]

[0012] 1. A pharmaceutical composition for the prevention or treatment of macular degeneration, comprising a peptide having the amino acid sequence of Sequence ID No. 1.

[0013] 2. In item 1 above, macular degeneration is age-related macular degeneration, and the pharmaceutical composition is otherwise accurate.

[0014] 3. In item 1 above, the pharmaceutical composition is a pharmaceutical composition that prevents or treats macular degeneration by reducing the degeneration of retinal pigment epithelial cells.

[0015] 4. A kit for the prevention or treatment of macular degeneration, comprising a pharmaceutical composition described in any of items 1 to 3 above, and instructions describing a method for the prevention or treatment of macular degeneration.

[0016] 5. In item 4 above, a method for preventing or treating macular degeneration is a kit comprising the step of administering a pharmaceutical composition to an individual who has developed or is at risk of developing macular degeneration.

[0017] 6. A health functional food containing a peptide having the amino acid sequence of Sequence ID No. 1, for the prevention or improvement of macular degeneration.

[0018] 7. In item 6 above, macular degeneration refers to age-related macular degeneration, a health functional food.

[0019] 8. In item 6 above, a health functional food is a health functional food that prevents or improves macular degeneration by reducing the degeneration of retinal pigment epithelial cells. [Effects of the Invention]

[0020] A pharmaceutical composition containing a peptide having the amino acid sequence of Sequence ID No. 1 of the present invention not only reduced cytopathogenesis in a retinal pigment epithelial cell model of age-related macular degeneration, but also showed inhibitory and / or therapeutic effects on retinal degeneration in an age-related macular degeneration-induced mouse model. Therefore, the pharmaceutical composition of the present invention is expected to be effective in the treatment, improvement, or prevention of macular degeneration.

[0021] The pharmaceutical composition and health functional food of the present invention contain GV1001 as an active ingredient, which has been confirmed to be safe from side effects in numerous clinical trials through toxicity testing. Therefore, it is expected to be useful in preventing, improving, or treating macular degeneration.

[0022] The pharmaceutical composition, kit, and functional food for health of the present invention are expected to provide economic or healthcare support to patients suffering from age-related macular degeneration in the future and their families.

[0023] By elucidating the mechanism of the pharmacological effect of GV1001 against age-related macular degeneration, the present invention is expected to contribute to the understanding of the pathophysiology related to the onset of age-related macular degeneration and become the driving force for future development of new therapeutic agents.

Brief Description of the Drawings

[0024] [Figure 1] Figure 1 shows the administration time of GV1001 and the experimental schedule of the pre-treatment animal experimental group used in the GV1001 short-term administration effect evaluation test. [Figure 2] Figure 2 shows the administration time of GV1001 and the experimental schedule of the post-treatment animal experimental group used in the GV1001 short-term administration effect evaluation test. [Figure 3] Figure 3 shows the drug administration time and the experimental schedule of the positive control group used in the GV1001 short-term administration effect evaluation test. [Figure 4] Figure 4 shows the administration time of GV1001 and the experimental schedule of the pre-treatment animal experimental group used in the GV1001 long-term administration effect evaluation test. [Figure 5] Figure 5 shows the administration time of GV1001 and the experimental schedule of the post-treatment animal experimental group used in the GV1001 long-term administration effect evaluation test. [Figure 6a] Figure 6 shows the results of confirming the effect of GV1001 in reducing reactive oxygen species. [Figure 6b] Figure 6 shows the results of confirming the effect of GV1001 in reducing reactive oxygen species. [Figure 7] Figure 7 shows the results of confirming the effect of GV1001 in reducing epithelial-mesenchymal transition. [Figure 8]Figure 8 shows the results of confirming the effects of short-term administration of GV1001 in a mouse model of age-related macular degeneration. [Figure 9] Figure 9 shows the results of confirming the effects of short-term administration of GV1001 in a mouse model of age-related macular degeneration. [Figure 10] Figure 10 shows the results of confirming the effects of long-term administration of GV1001 in a mouse model of age-related macular degeneration. [Figure 11] Figure 11 shows the results of confirming the effects of long-term administration of GV1001 in a mouse model of age-related macular degeneration. [Modes for carrying out the invention]

[0025] The present invention provides a pharmaceutical composition for the prevention or treatment of macular degeneration, comprising a peptide having the amino acid sequence of Sequence ID No. 1.

[0026] In the present invention, the peptide having the amino acid sequence of SEQ ID NO: 1 includes its functional equivalent. A "functional equivalent" refers to a peptide that, as a result of the addition, substitution, or deletion of amino acids, has at least 70%, 80%, 90%, or 95% sequence homology to the amino acid sequence of SEQ ID NO: 1 and exhibits substantially the same physiological activity as the peptide having the amino acid sequence of SEQ ID NO: 1. "Substantially the same physiological activity" refers to activity involved in the prevention, improvement, or treatment of macular degeneration.

[0027] In the present invention, "macular degeneration" includes age-related macular degeneration, senile macular degeneration, myopic macular degeneration, and macular dystrophy.

[0028] In the present invention, "age-related macular degeneration" includes dry macular degeneration and wet macular degeneration.

[0029] In one embodiment, the macular degeneration may be age-related macular degeneration.

[0030] In one embodiment, the macular degeneration may be dry macular degeneration.

[0031] In this invention, "prevention" means all actions that suppress or delay macular degeneration.

[0032] In this invention, "treatment" means all actions that improve or beneficially modify the symptoms of an individual suspected of having or who has developed macular degeneration.

[0033] In one embodiment, the pharmaceutical composition of the present invention can prevent or treat macular degeneration by reducing reactive oxygen species.

[0034] In one embodiment, the pharmaceutical composition of the present invention can prevent or treat macular degeneration by reducing the degeneration of retinal pigment epithelial cells.

[0035] In the present invention, "individual" means all animals, such as livestock and mice, that have developed or are likely to develop macular degeneration, and may include mammals, including humans, for example.

[0036] The pharmaceutical composition of the present invention may be provided as a pharmaceutical composition comprising an active ingredient alone, or as a pharmaceutical composition comprising one or more pharmaceutically acceptable carriers, excipients, or diluents.

[0037] Examples of carriers, excipients, or diluents that may be included in the pharmaceutical composition of the present invention include, but are not limited to, lactose, dextrose, sucrose, dextrin, maltodextrin, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, or mineral oil.

[0038] The present invention provides a kit for the prevention or treatment of macular degeneration, comprising a pharmaceutical composition for the prevention or treatment of macular degeneration and instructions describing a method for the prevention or treatment of macular degeneration.

[0039] In one embodiment, a method for preventing or treating macular degeneration may include the step of administering the pharmaceutical composition of the present invention to an individual who has developed or is at risk of developing macular degeneration.

[0040] In this invention, "administration" means introducing a predetermined substance into an individual using an appropriate method.

[0041] The administration route of the pharmaceutical composition of the present invention may be, but is not limited to, the oral cavity, intravenous, intramuscular, intraarterial, intramedullary, intradural, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, local, sublingual, or rectal.

[0042] In one embodiment, the composition of the present invention may be administered orally or parenterally.

[0043] When administering the composition of the present invention parenterally, it is preferable to select an injection method such as topical application to the skin, intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection, but is not limited to these.

[0044] The pharmaceutical composition of the present invention may be a solid dosage form for oral administration, such as a tablet, pill, powder, granule, or capsule.

[0045] The pharmaceutical composition of the present invention may be a liquid formulation for oral administration, such as a suspension, an oral solution, an emulsion, or a syrup.

[0046] The pharmaceutical composition of the present invention may be a formulation for parenteral administration, such as a sterile aqueous solution, a non-aqueous solvent, a suspension, an emulsion, a lyophilized formulation, or a suppository.

[0047] In one embodiment, a method for preventing or treating macular degeneration may include the step of administering a pharmaceutically effective amount of the pharmaceutical composition of the present invention to an individual who has developed or is at risk of developing macular degeneration.

[0048] In this invention, "pharmaceutically effective amount" means an amount sufficient to treat macular degeneration with a reasonable benefit / risk ratio applicable to medical treatment.

[0049] The pharmaceutically effective amount of the pharmaceutical composition of the present invention may be appropriately selected by those skilled in the art, depending on the severity of macular degeneration, the activity of the pharmaceutical composition, the sensitivity of the individual or patient to the pharmaceutical composition, the time of administration, the route of administration and excretion rate, the duration of treatment and concomitant drugs, and other factors well known in the medical field.

[0050] The pharmaceutical compositions of the present invention may be administered as individual therapeutic agents, in combination with other therapeutic agents, sequentially or simultaneously with conventional therapeutic agents, or administered as single or multiple doses, which can be easily determined by those skilled in the art.

[0051] The present invention provides a health functional food for the prevention or improvement of macular degeneration, comprising a peptide having the amino acid sequence of Sequence ID No. 1.

[0052] The health functional foods of the present invention refer to foods manufactured and / or processed in various forms to provide functions useful to the human body.

[0053] The health functional foods of the present invention may be included in various foods or pharmaceuticals known in the field.

[0054] The types of foods that may contain the health functional foods of the present invention are not particularly limited. For example, the health functional foods of the present invention may be contained in meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes.

[0055] The health functional foods of the present invention encompass all forms, including functional foods, nutritional supplements, health foods, and food additives, and these types of foods can be manufactured in various forms according to common methods known in the art. For example, health foods can be manufactured and consumed in the form of liquid drinks, or ingested in the form of granules, capsules, spherical tablets (such as balls), and powders, and can also be manufactured and ingested in the form of powders, capsules, soft capsules, tablets, gums, and sticky liquid compositions. Functional foods also include beverages (including alcoholic beverages), fruits and their processed foods (e.g., canned fruit, bottled fruit, jam, marmalade, etc.), fish, meats and their processed foods (e.g., ham, sausage, corned beef, etc.), breads and noodles (e.g., udon, soba, ramen, spaghetti, macaroni, etc.), fruit juices, various drinks, cookies, candies, dairy products (e.g., butter, cheese, etc.), edible vegetable oils and fats, margarine, vegetable protein, retort foods, frozen foods, herbal decoctions, and various seasonings (e.g., miso, soy sauce, sauces, etc.).

[0056] The health functional food of the present invention may further contain ingredients that are typically added during the manufacture of food, without departing from the ultimate objective of the present invention, such as proteins, carbohydrates, fats, other nutrients, seasonings, and flavorings.

[0057] The health functional food of the present invention may further contain various nutritional supplements, vitamins, electrolytes, flavorings, colorings, pectin acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated beverages, and the like.

[0058] The health functional food of the present invention may contain fruit pulp for the production of natural fruit juice, fruit juice beverages, and vegetable beverages. These components can be used individually or in combination.

[0059] The present invention will be described in detail below with reference to examples. However, the following examples are provided to aid in understanding the present invention, and the content of the present invention is not limited to these examples. [Examples]

[0060] Using retinal pigment epithelial cells and a mouse model of age-related macular degeneration, we confirmed that GV1001 has the effect of reducing damage to the retinal pigment epithelial layer. Furthermore, we conducted basic research to elucidate the molecular mechanism of the pharmacological action of GV1001 related to macular degeneration.

[0061] 1. Experimental Method 1.1. Synthesis of GV1001 A peptide consisting of 16 amino acids, having the structural formula shown in Chemical Formula 1 below and possessing the following Sequence ID No. 1 (GV1001), was synthesized from human telomerase.

[0062] [ka]

[0063] Peptide GV1001, sequence number 1, was prepared according to a conventional solid-phase peptide synthesis method. Specifically, the peptide was synthesized using ASP48S (Peptron, Inc., Daejeon, Korea) by coupling amino acids one by one from the C-terminus using the Fmoc solid-phase peptide synthesis (SPPS) method. The peptide used had the first amino acid of the C-terminus attached to the resin, as shown below. For example: NH2-Lys(Boc)-2-chloro-Trityl Resin NH2-Ala-2-chloro-Trityl Resin NH2-Arg(Pbf)-2-chloro-Trityl Resin

[0064] All amino acid raw materials used in peptide synthesis were protected with Fmoc at the N-terminus and all residues removed by acid, such as Trt, Boc, t-Bu (t-butylester), and Pbf (2,2,4,6,7-pentamethyl dihydro-benzofuran-5-sulfonyl). For example: Fmoc-Ala-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Glu(OtBu)-OH, Fmoc-Pro-OH, Fmoc-Leu-OH, Fmoc-Ile-OH, Fmoc-Phe-OH, Fmoc-Ser(tBu)-OH, Fmoc-Thr(tBu)-OH , Fmoc-Lys(Boc)-OH, Fmoc-Gln(Trt)-OH, Fmoc-Trp(Boc)-OH, Fmoc-Met-OH, Fmoc-Asn(Trt)-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Ahx-OH, Trt-Mercaptoacetic acid.

[0065] The coupling reagent used was HBTU[2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetamethylaminium hexafluorophosphate] / HOBt[N-Hydroxxybenzotriazole] / NMM[4-Methylmorpholine]. Piperidine in 20% DMF was used to remove Fmoc. The synthesized peptide was separated from the resin, and a cleavage cocktail [TFA(trifluoroacetic acid) / TIS(triisopropylsilane) / EDT(ethanedithiol) / H2O=92.5 / 2.5 / 2.5 / 2.5] was used to remove the protecting groups from the residues.

[0066] Using a solid support to which amino acid protecting groups were attached as starting amino acids, each amino acid was reacted with the support, washed with a solvent, and then deprotected. This process was repeated to synthesize each peptide. After the synthesized peptides were cleaved from the resin, they were purified by HPLC, their synthesis was confirmed by MS, and they were freeze-dried.

[0067] The specific synthesis process for GV1001 is as follows: 1) Coupling NH2-Lys(Boc)-2-chloro-Trityl Resin-protected amino acids (8 equivalents) and the coupling reagents HBTU (8 equivalents) / HOBt (8 equivalents) / NMM (16 equivalents) were dissolved in DMF and added. The mixture was then reacted at room temperature for 2 hours, and washed in the following order: DMF, MeOH, and DMF. 2) Fmoc deprotection Piperidine in 20% DMF was added, and the mixture was reacted twice at room temperature for 5 minutes each time. The mixture was then washed in the following order: DMF, MeOH, and DMF. 3) The basic peptide skeleton was constructed by repeating reactions 1 and 2. 4) Cleavage: The cleavage cocktail was added to the synthesized peptide resin, and the peptide was separated from the resin. 5) Cooling diethyl ether was added to the resulting mixture, and the obtained peptide was precipitated by centrifugation. 6) After purification by Prep-HPLC, the molecular weight was confirmed by LC / MS, and the product was frozen to produce a powder.

[0068] 1.2. Verification of the reduction of retinal pigment epithelial cell degeneration by GV1001 1) Establishment of a cell model for age-related macular degeneration Reactive oxygen species were generated by treating the retinal pigment epithelial cell line ARPE-19 with hydrogen peroxide (H2O2). We established a model cell line of degenerated retinal pigment epithelial cells that appear in age-related macular degeneration, and induced epithelial loss in these cells.

[0069] 2) Dosage and administration of the drug The experimental groups for verifying the cytopathic reduction effect of GV1001 were set up as shown in Table 1 below.

[0070] [Table 1]

[0071] *Before GV1001 treatment (pre-treatment), GV1001 was applied 2 hours prior, followed by treatment with H2O2 for 24 hours. *Post-treatment with GV1001 involved treating with H2O2 for 2 hours, followed by a 2-hour treatment with GV1001. *As a positive control drug for GV1001, metformin (Met) 1 mM, which has been shown to improve oxidative stress in retinal pigment epithelial cells treated with H2O2, was used. *All medications were used diluted in 0.9% physiological saline.

[0072] 3) Verification of the reduction of retinal pigment epithelial cell degeneration by GV1001 The details and methods of the study that investigated the effect of GV1001 on reducing cytopathogenesis in an H2O2-treated retinal pigment epithelial cell line model (ARPE-19) are as follows (Table 2 below).

[0073] [Table 2]

[0074] 1.3. Evaluation of the effects of short-term administration of GV1001 in a mouse model of age-related macular degeneration. 1) Establishment of an animal model for age-related macular degeneration Mice injected with sodium iodate (NaIO3) are used as a representative model for age-related macular degeneration. We established an age-related macular degeneration mouse model by inducing damage to retinal pigment epithelial cells by injecting NaIO3 into C57BL / 6 mice to induce specific oxidative stress.

[0075] 2) Dosage and administration of the drug To verify the effect of short-term administration of GV1001 on reducing retinal pigment epithelial degeneration, the animal experimental groups were set up as shown in Table 3 below.

[0076] [Table 3]

[0077] *NaIO3 was administered as a single intravenous injection (IV injection) at a dose of 20 mg / kg. *GV1001 was administered by subcutaneous injection (SC injection) three times a week at doses of 0.01, 0.1, 0.5, or 1.0 mg / kg. *As a pre-treatment, GV1001 was administered subcutaneously three times a week for two weeks, starting four days before NaIO3 administration, as shown in Figure 1. *Post-treatment with GV1001 involved subcutaneous injections of GV1001 three times over a one-week period starting 10 days after NaIO3 administration, as shown in Figure 2. *As a positive control drug for GV1001, metformin 4.0 mg / mL was used, which has been shown to improve the degeneration of the retinal pigment epithelium due to oxidative stress. It was administered in a schedule as shown in Figure 3, for 7 days prior to NaIO3 administration, diluted in drinking water and replaced with plain water. *All drugs except metformin were used after being diluted in physiological saline.

[0078] 3) Confirmation of the effect of GV1001 on reducing damage to the retinal pigment epithelium layer. To confirm whether GV1001 inhibits the disruption of tight junctions in the retinal pigment epithelium layer by NaIO3 administration, retinal pigment epithelium / choroid (RPE / choroid) samples were flat-mounted, and the junctions between epithelial cells were stained with phalloidin and observed under a confocal microscope.

[0079] 1.4. Evaluation of the effects of long-term administration of GV1001 in a mouse model of age-related macular degeneration. 1) Establishment of an animal model for age-related macular degeneration We established a mouse model of age-related macular degeneration by inducing damage to retinal pigment epithelial cells by injecting NaIO3 into C57BL / 6 mice to induce specific oxidative stress.

[0080] 2) Dosage and administration of the drug The dosage of GV1001 determined in a short-term efficacy evaluation trial was used for evaluating the efficacy of long-term administration. To verify the effect of long-term administration (3 months) of GV1001 on reducing retinal pigment epithelial degeneration, the animal experimental groups were set up as shown in Table 4 below.

[0081] [Table 4]

[0082] *NaIO3 was administered as a single dose of 20 mg / kg via tail vein injection. *GV1001 was administered subcutaneously three times a week at a dose of 0.1 or 1.0 mg / kg diluted in physiological saline. *As shown in Figure 4, GV1001 was administered subcutaneously three times a week for 12 weeks, starting 10 weeks before NaIO3 administration. *Post-treatment with GV1001, as shown in Figure 5, GV1001 was administered subcutaneously three times a week for 10 weeks, starting two weeks after NaIO3 administration.

[0083] 3) Confirmation of the effect of GV1001 on reducing damage to the retinal pigment epithelium layer. To confirm whether the disruption of tight junctions in the retinal pigment epithelium is inhibited by GV1001, the retinal pigment epithelium / choroid was flat-mounted, and the junctions between epithelial cells were stained with phalloidin. The degree of tight junction disruption was then observed using a confocal microscope.

[0084] 2. Experimental Results 2.1. Verification of the reduction of retinal pigment epithelial cell degeneration by GV1001 1) Reduction of reactive oxygen species by GV1001 Using DCF-DA, a staining sample for reactive oxygen species, changes in reactive oxygen species levels in retinal pigment epithelial cells (ARPE-19) induced by GV1001 were observed using a fluorescence microscope, and the results are shown in Figure 6. Oxidative stress was induced by H2O2, and DCF-DA fluorescence expression increased, but this decreased with metformin treatment in the positive control group.

[0085] Under oxidative stress conditions, GV1001 reduced DCF-DA fluorescence expression at a concentration of 0.01 μM pre-treatment and at concentrations of 0.1 μM and 10 μM post-treatment.

[0086] The increase in reactive oxygen species observed when retinal pigment epithelial cells are subjected to oxidative stress can be suppressed or reduced by GV1001. This confirms that GV1001 enables retinal pigment epithelial cells to counteract oxidative stress.

[0087] 2) Reduction of retinal pigment epithelial cell degeneration by GV1001 By observing changes in cadherin 1, an epithelial cell marker, and vimentin, a mesenchymal cell marker, using a confocal microscope, we confirmed the degree of epithelial-mesenchymal transition, which indicates degeneration of retinal pigment epithelial cells, and the results are shown in Figure 7.

[0088] It was confirmed that H2O2-induced oxidative stress promotes epithelial-mesenchymal transition by decreasing the expression of epithelial cell markers and increasing the expression of mesenchymal cell markers. When the positive control group was treated with metformin, epithelial-mesenchymal transition was reduced.

[0089] GV1001 reduced epithelial-mesenchymal transition at a concentration of 0.01 μM before treatment and at a concentration of 10 μM after treatment.

[0090] Epithelial-mesenchymal transition, observed when retinal pigment epithelial cells are subjected to oxidative stress, can be suppressed or reduced by GV1001. This confirms that GV1001 maintains or restores the epithelial properties of retinal pigment epithelial cells.

[0091] 2.2. Evaluation of the effects of short-term administration of GV1001 in a mouse model of age-related macular degeneration. To determine whether the disruption of tight junctions in the retinal pigment epithelial cell layer is inhibited by GV1001, the retinal pigment epithelial layer / choroid was flat-mounted, and the junctions between epithelial cells were stained with phalloidin and observed under a confocal microscope. The results are shown in Figures 8 and 9.

[0092] In the NaIO3-treated group, the tight junction structure of the retinal pigment epithelial cell layer was severely damaged, showing epithelial defects, confirming the successful establishment of a mouse model for macular degeneration. When treated with metformin, a positive control for GV1001, the tight junction structure was maintained.

[0093] GV1001 maintained the tight junction structure of the retinal pigment epithelial cell layer at 0.1 mg / kg pre-treatment and at 0.5 and 1.0 mg / kg post-treatment. This confirms that GV1001 maintains or restores the epithelial properties of retinal cells in a mouse model of age-related macular degeneration.

[0094] 2.3. Evaluation of the effects of long-term administration of GV1001 in a mouse model of age-related macular degeneration. To determine whether the disruption of tight junctions in the retinal pigment epithelium was reduced by long-term administration of GV1001, the retinal pigment epithelium / choroid was flat-mounted, and the junctions between epithelial cells were stained with phalloidin and observed under a confocal microscope. The results are shown in Figures 10 and 11.

[0095] In the NaIO3-treated group, the tight junction structure of the retinal pigment epithelial cell layer was severely damaged, showing epithelial defects, confirming that a successful mouse model of macular degeneration had been established.

[0096] As shown in Figure 10, in the pre-treatment stage, long-term administration of GV1001 at 0.1 mg / kg or 1.0 mg / kg resulted in good maintenance of the tight junction structure of the retinal pigment epithelium, no cell membrane destruction due to epithelial degeneration occurred, and one nucleus was observed per closed junction cell membrane.

[0097] As shown in Figure 11, in the post-treatment stage, long-term administration of GV1001 at 0.1 mg / kg or 1.0 mg / kg resulted in good maintenance of the tight junction structure of the retinal pigment epithelium, no cell membrane destruction due to epithelial degeneration occurred, and one nucleus was observed per closed junction cell membrane.

[0098] 3. Conclusion 3.1. Verification of the reduction of retinal pigment epithelial cell degeneration by GV1001 (1) Reduction of reactive oxygen species by GV1001 The increase in reactive oxygen species observed when retinal pigment epithelial cells are subjected to oxidative stress can be suppressed or reduced by GV1001. This means that GV1001 enables retinal pigment epithelial cells to counteract oxidative stress.

[0099] (2) Reduction of retinal pigment epithelial cell degeneration by GV1001 Epithelial-mesenchymal transition, observed when retinal pigment epithelial cells are subjected to oxidative stress, can be suppressed or reduced by GV1001. This means that GV1001 reduces the degeneration of retinal pigment epithelial cells and maintains or restores epithelial function.

[0100] 3.2. Evaluation of the effects of short-term administration of GV1001 in a mouse model of age-related macular degeneration. In a mouse model of age-related macular degeneration, compared to before administration of GV1001 (pre-treatment), short-term administration of GV1001 (post-treatment) reduced degeneration of the retinal pigment epithelium, and epithelial function was maintained or restored. This confirms that GV1001 exhibits excellent preventive and / or therapeutic effects against age-related macular degeneration.

[0101] 3.3. Evaluation of the effects of long-term administration of GV1001 in a mouse model of age-related macular degeneration. In a mouse model of age-related macular degeneration, compared to before administration of GV1001 (pre-treatment), long-term administration of GV1001 (post-treatment) reduced degeneration of the retinal pigment epithelium, and epithelial function was maintained or restored. This confirms that GV1001 exhibits excellent preventive and / or therapeutic effects against age-related macular degeneration.

Claims

1. A pharmaceutical composition for the prevention or treatment of macular degeneration, comprising a peptide having the amino acid sequence of Sequence ID No.

1.

2. The pharmaceutical composition according to claim 1, wherein the macular degeneration is age-related macular degeneration.

3. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition prevents or treats macular degeneration by reducing the degeneration of retinal pigment epithelial cells.

4. A pharmaceutical composition according to any one of claims 1 to 3, A kit for the prevention or treatment of macular degeneration, including instructions describing methods for the prevention or treatment of macular degeneration.

5. The kit according to claim 4, wherein the method for preventing or treating macular degeneration comprises the step of administering the pharmaceutical composition to an individual who has developed or is at risk of developing macular degeneration.

6. A health functional food containing a peptide having the amino acid sequence of Sequence ID No. 1, for the prevention or improvement of macular degeneration.

7. The health functional food according to claim 6, wherein the macular degeneration is age-related macular degeneration.

8. The health functional food according to claim 6, wherein the health functional food prevents or improves macular degeneration by reducing the degeneration of retinal pigment epithelial cells.

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