Use of targeting ets1 gene in prevention of acute anterior uveitis

Abstract

The application belongs to the technical field of biological medicine, and specifically discloses application of targeting ETS1 gene in prevention of acute anterior uveitis. The application first proves that ETS1 is involved in regulating the inflammatory process of acute anterior uveitis, and after overexpression of ETS1 in the eye by intravitreal injection of AAV-ETS1, an acute anterior uveitis model is established by LPS induction. The experimental results show that, compared with the LPS model group, AAV-ETS1 treatment can reduce the clinical inflammation score of LPS-induced acute anterior uveitis mice, reduce the anterior segment inflammation, and reduce the mRNA expression level of inflammation-related genes and the immunofluorescence signal intensity of inflammation-related proteins, thereby inhibiting the inflammatory response at multiple levels of clinical phenotype, transcription level and protein expression level. The application can be used for preparing a drug for preventing acute anterior uveitis, and can also be used for related drug screening and inflammation mechanism research, and has good application value and transformation potential.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically involving the application of targeting the ETS1 gene in the prevention of acute anterior uveitis. Background Technology

[0002] Acute anterior uveitis (AAU) is a common intraocular inflammatory disease that primarily affects the iris, ciliary body, and anterior chamber. Symptoms typically include redness, eye pain, photophobia, tearing, inflammatory cells in the anterior chamber, aqueous humor flare, and decreased visual function. AAU can be caused by various factors, including infection, endotoxin stimulation, autoimmune reactions, HLA-B27-related diseases, and abnormalities in the intraocular immune microenvironment. If the inflammation is not controlled promptly or recurs frequently, it can lead to posterior synechiae, secondary glaucoma, cataracts, macular edema, and irreversible visual impairment. Therefore, identifying novel molecular targets and interventions that can effectively prevent or treat acute anterior uveitis is of significant clinical importance.

[0003] Currently, the treatment of acute anterior uveitis mainly relies on topical corticosteroids, cycloplegic agents, and, when necessary, systemic immunosuppressive therapy. Glucocorticoids can rapidly suppress intraocular inflammation and are commonly used in the treatment of non-infectious uveitis. However, long-term or repeated use may cause adverse reactions such as increased intraocular pressure, cataracts, and increased risk of infection, and some patients experience relapse or inadequate treatment response. Valdes and Sobrin systematically summarized the options for glucocorticoid therapy in uveitis, pointing out that although glucocorticoids are an important anti-inflammatory tool, their safety and limitations in long-term use remain key issues in clinical treatment (Valdes LM, Sobrin L. Uveitis therapy: thecorticosteroid options[J]. Drugs Therefore, existing technologies still require the development of new strategies for the prevention and treatment of acute anterior uveitis with clear molecular mechanisms.

[0004] Lipopolysaccharide (LPS)-induced endotoxin-induced uveitis (EIU) is an important animal model for studying acute intraocular inflammation and acute anterior uveitis. LPS can induce acute intraocular inflammation, blood-eye barrier disruption, leukocyte infiltration, release of inflammatory factors, and anterior chamber inflammation by activating Toll-like receptor 4 (TLR4) and its downstream inflammatory signaling pathways. Li et al. reported that mouse endotoxin-induced uveitis can serve as a useful animal model for studying human acute anterior uveitis (Li Q, Peng B, Whitcup SM, et al. Endotoxin-induced uveitis in the mouse: susceptibility and genetic control[J]. Exp Eye Res , 1995, 61(5): 629-632.). Chu et al. further pointed out that rodent EIU is a TLR4-mediated acute organ inflammation model that can be used to simulate human anterior uveitis, analyze leukocyte migration, and evaluate novel anti-inflammatory treatments (Chu CJ, Herrmann P, Carvalho LS, et al. Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model[J]. Dis Model Mech , 2016, 9(4): 473-481. ).

[0005] In LPS-induced acute anterior uveitis, inflammatory factors, chemokines, adhesion molecules, and inflammatory enzymes such as TNF-α, IL-1β, IL-6, MCP-1, ICAM-1, iNOS, and COX-2 are often significantly upregulated and participate in anterior chamber inflammatory cell infiltration, tissue edema, and intraocular inflammation amplification. Therefore, in animal models of acute anterior uveitis, using clinical inflammation scoring to assess the degree of anterior segment inflammation, combined with real-time quantitative PCR or other mRNA detection methods to analyze the expression of inflammation-related genes, and using immunofluorescence to detect the expression and localization of inflammation-related proteins in ocular tissues, is a commonly used technical approach to evaluate disease severity and the effectiveness of drug intervention. Existing studies on LPS-induced uveitis have shown that LPS can induce increased intraocular inflammatory cell and protein exudation and upregulate the expression of inflammation-related genes such as TNF-α, IL-6, E-selectin, ICAM-1, and iNOS. Anti-inflammatory intervention can reduce these inflammatory markers.

[0006] ETS1, also known as E26 transformation-specific sequence 1 or Ets-1, is an important member of the ETS transcription factor family, widely involved in immune cell development, T cell differentiation, B cell function, inflammatory cytokine expression, and autoimmune homeostasis regulation. Notably, ETS1 plays a dual role in inflammation regulation, exhibiting both pro-inflammatory and anti-inflammatory effects. Regarding pro-inflammatory effects, ETS1 deficiency can reduce vascular inflammation and decrease inflammatory cell recruitment (Ets-1). - / - In a mouse model, ETS1 upregulates pro-inflammatory mediators such as MCP-1, VCAM-1, and MMPs, participating in pro-inflammatory responses following neointimal formation and vascular injury. Regarding anti-inflammation, ETS1 is a specific effector molecule of the Mek-Erk pathway, selectively responding to IL-4 to drive adipose tissue macrophages towards anti-inflammatory M2 polarization, alleviating adipose tissue inflammation and insulin resistance. ETS1 overexpression can reduce hyperoxia-induced inflammation and apoptosis by activating the Nrf2 / HO-1 pathway. Furthermore, ETS1 exerts a protective effect by inhibiting the differentiation of pathogenic Th17 cells; ETS1 expression is significantly reduced in skin-infiltrating lymphocytes from patients with severe atopic dermatitis; and T-cell-specific ETS1 knockout mice spontaneously exhibit severe atopic dermatitis-like symptoms. These studies demonstrate that ETS1 can exert pro-inflammatory or anti-inflammatory effects in different tissue microenvironments and cell types, with its function showing significant cell type and pathological background dependence.

[0007] Previous studies have shown that ETS1 is a negative regulator of Th17 cell differentiation and can inhibit Th17 / IL-17-related inflammatory responses, while the Th17 / IL-17 pathway is closely related to various autoimmune and inflammatory diseases. Moisan et al. reported that ETS1 deficiency can promote Th17 differentiation, indicating that ETS1 plays an important role in limiting inflammatory T cell responses (Moisan J, Grenningloh R, Bettelli E, et al. Ets-1 is a negative regulator of Th17 differentiation[J]. J Exp Med, 2007, 204(11): 2825-2835. ). Garrett-Sinha's review further points out that ETS1 is associated with genetic susceptibility to various autoimmune diseases and abnormal activation of immune cells. Low expression or abnormal function of ETS1 can lead to lymphocyte differentiation imbalance, autoantibody production and enhanced inflammatory response (Review 1: Garrett-Sinha LA, Kearly A, Satterthwaite AB. The role of the transcription factor Ets1 in lupus and other autoimmune diseases[J]. Crit Rev Immunol , 2016, 36(6):485-510; Review 2: Garrett-Sinha LA. An update on the roles of transcription factor Ets1 in autoimmune diseases[J]. WIREs Mech Dis , 2023, 15(6): e1627). However, there are currently no reports on the expression changes and functional roles of ETS1 in acute anterior uveitis, and it remains unclear whether ETS1 participates in regulating the inflammatory process of acute anterior uveitis and its specific mechanisms. Summary of the Invention

[0008] To address the shortcomings of existing technologies, this invention aims to provide the application of targeting the ETS1 gene in the prevention of acute anterior uveitis. This invention is the first to demonstrate that ETS1 participates in regulating the inflammatory process of acute anterior uveitis, achieving significant anti-inflammatory effects in an LPS-induced model through intraocular delivery of AAV-ETS1, providing a new target and strategy for gene therapy of acute anterior uveitis.

[0009] To achieve the above objectives, the present invention adopts the following technical solution: This invention uses a mouse model of acute anterior uveitis to evaluate the preventive effect of ETS1 on acute anterior uveitis. Specifically, AAV-ETS1 was first delivered into the mouse eye via intravitreal injection. After ETS1 was expressed in the eye, acute anterior uveitis was induced by intravitreal injection of LPS. Following LPS induction, mice exhibited anterior segment inflammatory responses, including anterior chamber inflammation, iris congestion, anterior chamber opacity, inflammatory cell infiltration, and increased expression of inflammation-related genes. The intervention effect of ETS1 on acute anterior uveitis was evaluated by comparing the inflammatory differences among the model group, the AAV empty vector control group, and the AAV-ETS1 treatment group.

[0010] In a preferred embodiment, the present invention uses clinical assessment indicators to evaluate the severity of acute anterior uveitis in mice. These clinical assessment indicators include corneal transparency, anterior chamber opacity, iris congestion, anterior chamber inflammatory cells, pupillary changes, and anterior segment inflammatory response.

[0011] In a preferred embodiment, the present invention uses an mRNA detection method to evaluate changes in the expression of inflammation-related genes in ocular tissue. The preferred mRNA detection method is real-time quantitative PCR. The inflammation-related genes detected include, but are not limited to, TNF-α, IL-1β, IL-6, F4 / 80, MCP-1, ICAM-1, VCAM-1, iNOS, COX-2, IL-17A, CXCL1, CXCL2, NLRP3, and NF-κB pathway-related genes.

[0012] In a preferred embodiment, the present invention employs immunofluorescence detection to evaluate the expression and localization of inflammation-related proteins in mouse eye tissue. Detection indicators include, but are not limited to, TNF-α, IL-1β, IL-6, iNOS, COX-2, ICAM-1, CD45, CD68, Iba1, F4 / 80, Ly6G, NF-κB p65, and NLRP3.

[0013] The experimental results of this invention show that, compared with the LPS model group, the clinical score of anterior uveitis and the anterior chamber inflammation were reduced in the AAV-ETS1 treatment group, indicating that AAV-ETS1 can alleviate the clinical inflammatory manifestations of LPS-induced acute anterior uveitis. The expression of inflammation-related genes in ocular tissue decreased after AAV-ETS1 treatment, indicating that the ETS1 gene can inhibit the inflammatory transcriptional response in acute anterior uveitis. The immunofluorescence signal of inflammation-related proteins was weakened and the infiltration of inflammatory cells was reduced in the AAV-ETS1 treatment group, indicating that AAV-ETS1 can inhibit the inflammatory response of acute anterior uveitis at both the protein expression and tissue localization levels.

[0014] In summary, this invention demonstrates that intraocular delivery of the ETS1 gene can reduce the clinical inflammation score in mice with LPS-induced acute anterior uveitis, inhibit the expression of inflammation-related gene mRNA, and reduce the expression of inflammation-related proteins. This indicates that ETS1 participates in regulating the inflammatory process of acute anterior uveitis, and that the ETS1 protein, the nucleic acid molecule encoding ETS1, or an expression vector containing said nucleic acid molecule can be used to prepare drugs for the prevention of acute anterior uveitis.

[0015] Therefore, the first objective of this invention is to provide the use of ETS1 in the preparation of a medicament for the prevention of acute anterior uveitis.

[0016] Preferably, the ETS1 exerts its anti-inflammatory effect by downregulating the expression of inflammation-related genes and / or inflammation-related proteins.

[0017] Preferably, the inflammation-related genes include one or more of TNF-α, IL-1β, IL-6, and F4 / 80.

[0018] Preferably, the inflammation-related proteins include Iba1 and F4 / 80.

[0019] Preferably, the drug has ETS1 protein, nucleic acid molecule encoding ETS1, or expression vector containing said nucleic acid molecule as active ingredient, and contains pharmaceutically acceptable excipients.

[0020] Preferably, the expression vector is a viral vector.

[0021] More preferably, the expression vector is an adeno-associated virus vector, a lentiviral vector, or an adenovirus vector.

[0022] More preferably, the expression vector is an adeno-associated virus vector.

[0023] Preferably, the dosage form of the drug is an injection.

[0024] Preferably, the injection includes an injection solution and a lyophilized powder for injection.

[0025] Preferably, the drug is administered via intraocular injection.

[0026] Preferably, the intraocular injection includes intravitreal injection, anterior chamber injection, or subretinal injection.

[0027] Preferably, the drug exerts its preventive effect by upregulating the expression level of ETS1 in the eye.

[0028] A second object of the present invention is to provide a pharmaceutical composition for the prevention of acute anterior uveitis, comprising a vector overexpressing the ETS1 gene and pharmaceutically acceptable excipients.

[0029] Preferably, the vector for overexpressing the ETS1 gene is AAV9-SLRSPPS-ETS1.

[0030] Compared with the prior art, the present invention has the following beneficial effects: (1) This invention is the first to demonstrate that ETS1 participates in regulating the inflammatory process of acute anterior uveitis, providing a new molecular intervention target for acute anterior uveitis. By constructing an AAV-ETS1 intraocular delivery system, this invention demonstrates that ETS1 has a significant inhibitory effect on acute intraocular inflammatory response in an LPS-induced acute anterior uveitis model, filling the research gap of ETS1 in the field of intraocular inflammation regulation.

[0031] (2) A local gene therapy strategy for intraocular use is provided. This invention achieves stable local expression of ETS1 in the eye by injecting AAV-ETS1 into the vitreous cavity. Compared with existing systemic administration methods, it has the potential advantages of high intraocular drug concentration, low systemic exposure, and strong local targeting, which can reduce systemic adverse reactions.

[0032] (3) Clear therapeutic effect. This invention systematically evaluated the intervention effect of ETS1 on acute anterior uveitis from three levels: clinical phenotype, transcriptional level, and protein localization: AAV-ETS1 can reduce the clinical inflammation score of LPS-induced acute anterior uveitis mice and alleviate anterior segment inflammation; it can reduce the mRNA expression level of inflammation-related genes in ocular tissue; it can weaken the immunofluorescence signal of inflammation-related proteins and reduce inflammatory cell infiltration. The above multidimensional evidence corroborates each other, indicating that ETS1 has a significant inhibitory effect on acute anterior uveitis.

[0033] (4) This invention provides a new technological basis for reducing glucocorticoid dependence. Current treatments for acute anterior uveitis mainly rely on glucocorticoids, but long-term use can lead to side effects such as increased intraocular pressure, cataracts, and increased risk of infection. The ETS1 gene therapy strategy provided by this invention can serve as a potential alternative or adjunctive treatment, providing experimental evidence for developing novel treatments that reduce glucocorticoid dependence.

[0034] (5) It has good application and transformation potential. This invention can not only be used to prepare drugs for the prevention of acute anterior uveitis, but also for the screening of drugs related to acute anterior uveitis, the study of inflammatory pathway mechanisms, and the optimization and evaluation of intraocular gene delivery systems. It has broad application value in the field of ophthalmic gene therapy. Attached Figure Description

[0035] Figure 1 Schematic diagram of drug administration and experimental protocol for mouse acute anterior uveitis model.

[0036] Figure 2 Detection of AAV-ETS1 expression in mouse eyes (n=4). All data are presented as mean ± standard error (SE). ****: p < 0.0001.

[0037] Figure 3 Slit-lamp observation and clinical inflammation scoring of the ocular surface in mice with acute anterior uveitis. Figure 3 A in the figure represents slit-lamp observation photographs of the ocular surface of mice in each experimental group (scale bar: 400 μm). Figure 3 Figure B shows the statistical graph of clinical inflammation scores in mice of each experimental group (n=6). All data are presented as mean ± standard error (SE). ****: p < 0.0001.

[0038] Figure 4Real-time quantitative PCR results of relative expression levels of TNF-α, IL-1β, IL-6, and F4 / 80 mRNA in ocular tissues of mice in each experimental group (n=4). All data are presented as mean ± standard error (SE). ****: p < 0.0001.

[0039] Figure 5 Immunofluorescence detection of F4 / 80 and Iba1 expression in mouse ocular tissue. Figure 5 In the figure, A represents immunofluorescence staining micrographs of F4 / 80 and Iba1 in the ocular tissues of mice in each experimental group (scale bar: 200 μm). Figure 5 Figure B shows the statistical charts for F4 / 80 and Iba1 positive areas. F4 / 80 positive area statistics are for the AAV-CTRL-PBS group (n=8), AAV-CTRL-LPS group (n=8), and AAV-ETS1-LPS group (n=10); Iba1 positive area statistics are for each group (n=8). All data are presented as mean ± standard error (SE). ****: p < 0.0001. Detailed Implementation

[0040] To make the technical problem to be solved and the technical solution of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only for explaining the invention and are not intended to limit the invention.

[0041] Example 1: Preparation of AAV-ETS1 carrier The AAV-ETS1 used in this embodiment is a recombinant adeno-associated virus vector (purchased from Shandong Weizhen Biotechnology) carrying the expression sequence of the mouse Ets1 gene (Gene ID: 23871), the nucleotide sequence of which is shown in SEQ ID NO. 1. Since mouse Ets1 and human ETS1 share high sequence homology, especially the highly conserved ETS1 DNA-binding domain and functional regulatory region, the function of the AAV viral expression protein using the mouse Ets1 CDS region can reflect the biological effects mediated by the human ETS1 CDS region.

[0042] The recombinant adeno-associated virus vector includes a promoter, an Ets1 coding sequence, a polyA transcription termination sequence, and AAV-related packaging elements. The promoter is the Cdh5 promoter, the nucleotide sequence of which is shown in SEQ ID NO.2, and it can drive the expression of the target gene in intraocular tissues. The polyA transcription termination sequence is shown in SEQ ID NO.3. The AAV serotype is AAV9, suitable for intraocular delivery. The capsid is an AAV9-SLRSPPS capsid, constructed and packaged by Shandong Weizhen Biotechnology Co., Ltd. based on a publicly available capsid modification strategy. This modification strategy originates from the AAV9 Cap VR-VIII region peptide display technology reported by Varadi K et al. (Varadi K, Michelfelder S, Korff T, et al. Novel random peptide libraries displayed on AAV serotype 9 for selection of endothelial cell-directed gene transfer vectors[J]. Gene Ther , 2012, 19(8):800-809. ), specifically, the AAV9-SLRSPPS heptapeptide sequence was inserted near A589 of the VP3 domain of the AAV9 Cap protein, and the AAV9-SLRSPPS-Cap construct was obtained by optimizing the insertion region. Compared with the wild-type AAV9-Cap, amino acids AQA at positions 587-589 were mutated to GQAG, amino acids QAQ at positions 590-592 were mutated to QAA, and seven amino acids of SLRPPS were inserted between amino acids 589 and 590. The amino acid sequence of the AAV9-SLRSPPS capsid is shown in SEQ ID NO.4. The target gene and control virus were packaged using the modified AAV9-SLRSPPS-Cap plasmid, and the viral titer was 1×10 13 vg / mL. The AAV-ETS1 was delivered into the mouse eye via intravitreal injection, allowing ETS1 to be expressed in the ocular tissue. The control virus used was the AAV9-SLRSPPS empty vector (hereinafter labeled AAV-CTRL).

[0043] Example 2: Therapeutic effect of AAV-ETS1 on LPS-induced acute anterior uveitis in mice 1. Laboratory animals and grouping Healthy 8-week-old adult C57BL / 6 mice were selected as experimental animals and randomly divided into three groups: AAV-CTRL+PBS group, AAV-CTRL+LPS model group, and AAV-ETS1+LPS model treatment group. Among them: AAV-CTRL+PBS group: Empty vector AAV was injected into the vitreous cavity, without LPS induction, and an equal volume of PBS was administered; AAV-CTRL+LPS model group: First, inject empty vector AAV into the vitreous cavity, then inject LPS into the vitreous cavity to establish an acute anterior uveitis model. AAV-ETS1+LPS model treatment group: AAV-ETS1 was injected intravitreally first, and after ETS1 was expressed in the eye, LPS was injected intravitreally to induce acute anterior uveitis.

[0044] 2. Intravitreal injection of AAV-ETS1 Mouse eyeballs were fixed under a microscope, and AAV-ETS1 was injected into the mouse eye via a microsyringe inserted behind the limbus into the vitreous cavity. The injection volume was 1 μL / eye, and the viral titer was 1 × 10⁻⁶. 13 vg / mL, which means the dose administered to one eye is 1×10 10 vg.

[0045] After injection, the ocular condition of mice was observed, and animals with severe hemorrhage, lens damage, or significant mechanical injury were excluded. Two weeks after intravitreal injection of AAV-ETS1, once ETS1 was stably expressed in the eye, an acute anterior uveitis model was established by LPS induction. Figure 1 ).

[0046] 3. Establishment of an LPS-induced acute anterior uveitis model After AAV-ETS1 was expressed in the mouse eye, an acute anterior uveitis model was established by intravitreal injection of LPS. The injection volume of LPS was 1 μL / eye, and the concentration of LPS was 15 ng / μL. Twenty-four hours after LPS injection, mice exhibited an acute anterior segment inflammatory response, including increased inflammatory cells in the anterior chamber, anterior chamber opacity, iris congestion, enhanced anterior segment inflammatory response, and upregulation of the expression of inflammation-related genes and proteins.

[0047] 4. Statistical Analysis Experimental data are expressed as mean ± standard deviation. One-way ANOVA was used for comparisons among multiple groups, and LSD-t test (or Tukey's method, Bonferroni method) was used for pairwise comparisons between groups. A p-value < 0.05 was considered statistically significant.

[0048] 5. Clinical inflammation scoring evaluation Twenty-four hours after LPS injection, the anterior segment inflammation in mice was observed under a slit-lamp microscope, and the severity of acute anterior uveitis was assessed using a clinical inflammation scoring system. Observational indicators included corneal transparency, anterior chamber flare, anterior chamber inflammatory cells, iris congestion, and pupillary morphology changes. A 0-7 scoring system was used, with higher scores indicating more severe inflammation. Clinical scoring was completed independently by at least two observers under blinded conditions to minimize subjective bias.

[0049] The results showed that, compared with the LPS model group, the clinical score of anterior uveitis in mice treated with AAV-ETS1 was reduced, indicating that AAV-ETS1 can alleviate the clinical inflammatory manifestations of LPS-induced acute anterior uveitis. Figure 3 ).

[0050] 6. Detection of inflammation-related gene mRNA Twenty-four hours after LPS injection, mouse eye tissues, including the iris-ciliary body, anterior segment, retina, or whole eye, were harvested. Total RNA was extracted, reverse transcribed into cDNA, and the mRNA expression levels of inflammation-related genes TNF-α, IL-1β, F4 / 80, and IL-6 were detected using real-time quantitative PCR. Simultaneously, the ETS1 mRNA expression level was detected to verify the expression effect of AAV-ETS1 in the mouse eye.

[0051] The results showed that, compared with the AAV-CTRL group, the mRNA expression level of ETS1 in the eyes of mice in the AAV-ETS1 group was significantly increased, suggesting that AAV-ETS1 successfully mediated the overexpression of ETS1 in the eye. Figure 2 ).

[0052] Furthermore, compared with the LPS model group, the AAV-ETS1 treatment group showed significantly reduced mRNA expression levels of inflammation-related genes such as TNF-α, IL-1β, F4 / 80, and IL-6. Figure 4 This indicates that AAV-ETS1 can inhibit the inflammatory transcriptional response in acute anterior uveitis.

[0053] 7. Immunofluorescence detection of inflammation-related protein expression Mouse eye tissue was harvested 24 hours after LPS injection, and then fixed, dehydrated, embedded, and frozen sectioned. Immunofluorescence staining was then used to detect the expression and localization of inflammation-related proteins in the eye tissue, including Iba1 and F4 / 80.

[0054] The results showed that, compared with the LPS model group, the immunofluorescence signals of inflammation-related proteins Iba1 and F4 / 80 in the ocular tissue of the AAV-ETS1 treatment group were significantly reduced, and the infiltration of inflammatory cells was decreased. Figure 5This indicates that AAV-ETS1 can inhibit LPS-induced acute anterior uveitis inflammatory response at both the protein expression and tissue localization levels.

[0055] The above detailed description is a specific description of the embodiments of the present invention. These embodiments are not intended to limit the patent scope of the present invention. All equivalent implementations or modifications that do not depart from the present invention should be included in the patent scope of this case.

Claims

1. The application of an adeno-associated virus vector overexpressing ETS1 in the preparation of a drug for the prevention of acute anterior uveitis, characterized in that, The nucleotide sequence of ETS1 is shown in SEQ ID NO.

1.

2. The application according to claim 1, characterized in that, The ETS1 exerts its anti-inflammatory effect by downregulating the expression of inflammation-related genes and / or inflammation-related proteins.

3. The application according to claim 2, characterized in that, The inflammation-related genes include one or more of TNF-α, IL-1β, IL-6, and F4 / 80.

4. The application according to claim 2, characterized in that, The inflammation-related proteins include Iba1 and F4 / 80.

5. The application according to any one of claims 1-4, characterized in that, The drug is in the form of an injection.

6. The application according to claim 5, characterized in that, The injectables include injection solutions and lyophilized powder injections.

7. The application according to any one of claims 1-4, characterized in that, The drug is administered via intraocular injection.

8. The application according to claim 7, characterized in that, The intraocular injection includes intravitreal injection, anterior chamber injection, or subretinal injection.

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