Application of indoleacetic acid in preparation of medicine or food for treating optic nerve injury

Abstract

The invention relates to a compound indoleacetic acid and application of the compound indoleacetic acid as an active ingredient in preparation of medicines or foods for treating optic nerve injury, and the indoleacetic acid is given in vivo, so that the number of retinal ganglion cells and the thickness of a retinal nerve fiber layer are favorably maintained, and activation of retinal microglial cells is inhibited; retina inflammation pathway activation and inflammatory mediator expression are inhibited, so that the visual function is protected.

Description

Technical Field

[0001] The present invention relates to a new use of a known product, in particular to a compound having biological effects in protecting retinal ganglion cells, protecting visual function, inhibiting microglial activation, inhibiting activation of retinal inflammatory pathways and expression of inflammatory mediators, and its use as an active ingredient in the manufacture of drugs, medical devices and foods. Background Art

[0002] Glaucoma is a group of diseases characterized by characteristic optic atrophy and visual field loss, with elevated intraocular pressure being the primary risk factor. According to statistics, glaucoma is the world's leading irreversible cause of blindness, with the global prevalence projected to reach 111.8 million by 2040. This places a significant medical and economic burden on patients, necessitating an urgent need for breakthroughs in treatment.

[0003] Numerous compounds, proteins or nucleic acids have been successfully developed and applied in the treatment of glaucoma, and numerous medical devices are also used in the clinical diagnosis and treatment of glaucoma.

[0004] Indoleacetic acid, first discovered in plants by Frits Warmolt Went in 1928, is the most common auxin in plants. Current research suggests that indoleacetic acid has protective effects in mouse models of liver cancer and chronic obstructive pulmonary disease, and alleviates liver oxidative stress and inflammation in a mouse model of non-alcoholic fatty liver disease. However, the role of indoleacetic acid in glaucoma and related ocular neurodegenerative diseases has not yet been reported. Summary of the Invention

[0005] One object of the present invention is to provide a compound which is used as an active ingredient for protecting visual function, protecting retinal nerve cells, regulating microglial activation and regulating inflammatory factor expression, thereby facilitating the treatment of optic nerve damage.

[0006] Another object of the present invention is to provide a compound, indoleacetic acid, which is used as an active ingredient to protect optic nerve damage and is beneficial for treating glaucoma.

[0007] Another object of the present invention is to provide a drug comprising the compound indoleacetic acid for use in treating glaucoma.

[0008] Another object of the present invention is to provide a medical device comprising the compound indoleacetic acid for use in treating glaucoma.

[0009] Another object of the present invention is to provide a food containing indoleacetic acid as an active ingredient for use in treating glaucoma.

[0010] Indoleacetic acid was first discovered in plants by Frits Warmolt Went in 1928 and is the most common auxin in plants. However, a growing number of studies have also shown that indoleacetic acid is also present in mammals, with the main sources including endogenous and exogenous. Among them, endogenous indoleacetic acid may be produced by the decarboxylation of tryptophan or the oxidative deamination of tryptophan in cells, while exogenous indoleacetic acid is usually produced by microorganisms in the mammalian intestine. Current studies have shown that indoleacetic acid has a protective effect on liver cancer model mice, chronic obstructive pulmonary disease model mice, etc., and can alleviate liver oxidative stress and inflammatory response in non-alcoholic fatty liver disease mouse model.

[0011] Administration of indoleacetic acid to glaucoma model mice maintained the number of retinal ganglion cells and the thickness of the retinal nerve fiber layer, inhibited the activation of retinal microglia, inhibited the activation of retinal inflammatory pathways and the expression of inflammatory mediators, and thus protected visual function.

[0012] A bioreactor has microparticles formed of lipid membranes or vesicles, which contain nucleic acids and produce indoleacetic acid from the nucleic acids.

[0013] A microorganism that produces indoleacetic acid.

[0014] Another microorganism has been genetically edited to contain foreign genetic material and thus produce indoleacetic acid.

[0015] Another microorganism comprises a plasmid comprising exogenous genetic material and is regulated to produce indoleacetic acid.

[0016] In a specific embodiment, the exogenous genetic material is a Bacteroides fragilis indoleacetic acid production gene.

[0017] In another specific embodiment, the exogenous genetic material is more than 97% homologous to the indoleacetic acid-producing gene of Bacteroides fragilis.

[0018] In another specific embodiment, the exogenous genetic material is more than 95% homologous to the indoleacetic acid-producing gene of Bacteroides fragilis.

[0019] In another specific embodiment, the exogenous genetic material is more than 93% homologous to the indoleacetic acid-producing gene of Bacteroides fragilis.

[0020] In another specific embodiment, the exogenous genetic material is more than 90% homologous to the indoleacetic acid-producing gene of Bacteroides fragilis.

[0021] In another specific embodiment, the exogenous genetic material is more than 85% homologous to the indoleacetic acid-producing gene of Bacteroides fragilis.

[0022] In another specific embodiment, the exogenous genetic material is more than 80% homologous to the indoleacetic acid-producing gene of Bacteroides fragilis.

[0023] In another specific embodiment, the exogenous genetic material is more than 75% homologous to the indoleacetic acid-producing gene of Bacteroides fragilis.

[0024] In another specific embodiment, the exogenous genetic material is more than 70% homologous to the indoleacetic acid-producing gene of Bacteroides fragilis.

[0025] Bacteroides fragilis was purchased from Micro-Biotech (Shanghai) Co., Ltd., with the accession number: ATCC25285.

[0026] Food (additive) or medicine is made with indoleacetic acid as the active ingredient and delivered into the body to alleviate retinal damage and retinal ganglion cell loss, including but not limited to maintaining the number of retinal ganglion cells, maintaining the thickness of the retinal nerve fiber layer, improving visual function, reducing retinal microglia activation, reducing retinal inflammatory pathway activation and inflammatory mediator expression.

[0027] Food (additive) or medicine is made with a bioreactor that produces indoleacetic acid as the active ingredient and delivered into the body (such as the gastrointestinal tract) to alleviate retinal damage and retinal ganglion cell loss, including but not limited to maintaining the number of retinal ganglion cells, maintaining the thickness of the retinal nerve fiber layer, improving visual function, reducing retinal microglia activation, reducing retinal inflammatory pathway activation and inflammatory mediator expression.

[0028] Food (additives) or drugs are made with microorganisms that produce indoleacetic acid as active ingredients and delivered to the gastrointestinal tract to reduce optic nerve damage, help reduce the loss of retinal ganglion cells, inhibit retinal microglial activation, inhibit retinal neuroinflammation, and protect visual function.

[0029] The indoleacetic acid of the present invention is allowed to act on cells in vitro or in vivo to achieve the purpose of promoting optic nerve repair, which should be understood as the use of indoleacetic acid as a drug for the purpose of the present invention.

[0030] Indoleacetic acid is mixed with other excipients to prepare a medicine (preparation) for treating optic nerve damage diseases (such as glaucoma).

[0031] These pharmaceutical excipients can be those conventionally used in various preparations, such as but not limited to isotonic agents, buffers, flavoring agents, excipients, fillers, binders, disintegrants and lubricants; they can also be selected for compatibility with the substances, such as emulsifiers, solubilizers, antibacterial agents, analgesics and antioxidants. Such excipients can effectively improve the stability and solubility of the compounds contained in the composition or change the release rate and absorption rate of the compounds, thereby improving the metabolism of various compounds in the organism and enhancing the administration effect of the composition.

[0032] In aqueous injections, excipients generally include isotonic agents and buffers, as well as necessary emulsifiers (such as Tween-80, Pluronic, and Poloxamer), solubilizers, and antibacterial agents. In addition, other pharmaceutically acceptable excipients may also be included, such as antioxidants, pH regulators, and analgesics.

[0033] Excipients used to prepare oral liquid preparations generally include solvents, as well as necessary flavoring agents, antibacterial agents, emulsifiers and colorants.

[0034] The excipients used to make tablets generally include fillers (such as starch, powdered sugar, dextrin, lactose, compressible starch, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate and mannitol), binders (such as ethanol, starch slurry, sodium carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, gelatin solution, sucrose solution and aqueous or alcoholic solution of polyvinyl pyrrolidone), disintegrants (such as dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked polyvinyl pyrrolidone and cross-linked sodium carboxymethyl cellulose) and lubricants (such as magnesium stearate, micronized silica gel, talc, hydrogenated vegetable oil, polyethylene glycol 4,000, polyethylene glycol 6,000 and magnesium lauryl sulfate), etc.

[0035] The auxiliary materials used to prepare emulsions are generally water, oil (such as fatty acids), emulsifiers, and necessary preservatives and flavoring agents.

[0036] The excipients used to prepare granules are similar to those used for tablets, but the granulation process is different. The granules are mixed with a glidant as needed and then filled into capsules to produce capsules.

[0037] Various excipients and compounds are formulated into dosage forms that facilitate drug delivery, such as, but not limited to, aqueous solution injections, powder injections, pills, powders, tablets, patches, suppositories, emulsions, creams, gels, granules, capsules, aerosols, sprays, powder aerosols, sustained-release agents, and controlled-release agents. Furthermore, excipients such as, but not limited to, gelatin, albumin, chitosan, polyether and polyester polymers, such as, but not limited to, polyethylene glycol, polyurethane, polycarbonate, and copolymers thereof, may be used to achieve specific drug delivery purposes or methods, such as sustained-release, controlled-release, and pulse delivery. The so-called "facilitating drug delivery" primarily includes, but not limited to, enhancing therapeutic efficacy, increasing bioavailability, reducing toxic side effects, and improving patient compliance.

[0038] The indoleacetic acid of the present invention is combined with other excipients, such as chemical coupling, to further improve the efficacy of the compound, the in vivo release period, and the duration of administration. These excipients are usually polymers, such as polyesters, polyethers, and polyamides.

[0039] Medical devices are made of indoleacetic acid as the active ingredient carried in medical materials to deliver indoleacetic acid into the body to alleviate retinal damage and retinal ganglion cell loss, including but not limited to maintaining the number of retinal ganglion cells, maintaining the thickness of the retinal nerve fiber layer, improving visual function, reducing retinal microglia activation, and reducing retinal inflammatory pathway activation and inflammatory mediator expression.

[0040] Indoleacetic acid is loaded or coated onto scaffold materials to create medical devices for repairing optic nerve damage. Common scaffold materials include PLA, PLGA, GelMA, chitosan, and γPGA. It can also be mixed with biocompatible, degradable materials to create microneedles and microneedle arrays, or loaded into metal microneedles to create microneedle chips. Upon penetration of the skin, the indoleacetic acid is released into the dermis, forming microspheres or gels that adhere to the mucosa, enhancing optic nerve repair. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 Figure 28 shows the verification of retinal ganglion cell protection in mice on day 28 after glaucoma modeling; a is a typical field of view of a fluorescent confocal microscope of a mouse retinal flatbed (scale bar = 30 μm), with β-III tubulin (red) marking retinal ganglion cells; b is a schematic diagram of the position of the field of view in figure a; c is a statistical diagram of the retinal ganglion cell survival rate of mice in each group; * indicates that there is a statistical difference between the two groups, p < 0.05; *** indicates that there is a statistical difference between the two groups, p < 0.001;

[0042] Figure 2The figure shows the verification of the protection of the retinal nerve fiber layer thickness and retinal ganglion cell number in mice on day 28 after glaucoma modeling; among them, a is a typical visual field of hematoxylin-eosin staining of retinal sections of mice in each group (scale bar = 50 μm), b is a statistical diagram of the number of retinal ganglion cell layer (GCL) cells in each group, c is a statistical diagram of the retinal nerve fiber layer (RNFL) thickness; d is a statistical diagram of the inner plexiform layer (IPL) thickness, * indicates that there is a statistical difference between the two groups, p < 0.05, ** indicates that there is a statistical difference between the two groups, p < 0.01, *** indicates that there is a statistical difference between the two groups, p < 0.001;

[0043] Figure 3 Figure 2 is a graph showing the results of the validation of indoleacetic acid for improving the visual function of glaucoma model mice; a is a statistical graph showing the number of mice in each group who first stepped onto the cliff side in the visual cliff experiment; b is a statistical graph showing the total time that mice in each group stayed on the cliff side in the visual cliff experiment. * indicates a statistically significant difference between the two groups, p < 0.05; *** indicates a statistically significant difference between the two groups, p < 0.001;

[0044] Figure 4 Figure 2 shows the results of the validation of indoleacetic acid inhibiting retinal microglial activation in glaucoma model mice; a is a typical field of view of a fluorescent confocal microscope of a mouse retinal flatbed (scale bar = 50 μm), with Iba1 (green) labeling microglia; b is a statistical graph of the relative number of Iba1-positive cells in each group; c is a statistical graph of the relative cumulative optical density of Iba1; *** indicates a statistically significant difference between the two groups, p < 0.001;

[0045] Figure 5Figure 2 is the result of the verification of indoleacetic acid inhibiting the activation of retinal neuroinflammatory pathway and expression of inflammatory mediators in glaucoma model mice; among them, a is the protein blotting diagram of iNOS, p-NFκB and NFκB in each group, b is the quantitative statistical diagram of the p-NFκB protein expression level in each group normalized by NFκB, c is the quantitative statistical diagram of the iNOS protein expression level in each group normalized by β-tubulin, d is the protein blotting diagram of TNF-α, IL-1β and IL-6 in each group, e is the quantitative statistical diagram of the TNF-α protein expression level in each group normalized by β-tubulin, f is the quantitative statistical diagram of the IL-1β protein expression level in each group normalized by β-tubulin, g is Quantitative statistical graph of IL-6 protein expression level in each group normalized by β-tubulin; h is the relative quantitative statistical graph of TNF-α, IL-1β, IL-6 and iNOS mRNA expression in each group; i is the immunofluorescence graph of the localization and relative expression of TNF-α, IL-1β, IL-6 and iNOS in the GCL (ganglion cell layer), IPL (inner plexiform layer) and INL (inner nuclear layer) of retinal sections of mice in each group (scale bar = 50 μm); * indicates that there is a statistical difference between the two groups, p < 0.05; ** indicates that there is a statistical difference between the two groups, p < 0.01; *** indicates that there is a statistical difference between the two groups, p < 0.001. DETAILED DESCRIPTION

[0046] The technical solution of the present invention is described in detail below with reference to the accompanying drawings. The embodiments of the present invention are intended only to illustrate the technical solution of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solution of the invention may be modified or replaced with equivalents without departing from the spirit and scope of the technical solution of the present invention, and all such modifications or equivalents should be included in the scope of the claims of the present invention.

[0047] Unless otherwise specified, all other reagents used in the examples of the present invention were purchased from Biyuntian Company.

[0048] In the mouse experiments in this example, 6- to 8-week-old wild-type C57BL / 6J mice were selected and raised under standard conditions.

[0049] 1) Establishment of glaucoma mouse model

[0050] Male C57BL / 6J mice aged 6-8 weeks, weighing 18-25 g, were purchased from Shanghai Jiesijie Experimental Animal Co., Ltd. The mice were randomly divided into three groups: control group (Control group), glaucoma model group (MB group), and glaucoma model combined with indoleacetic acid intervention group (MB+IAA). The glaucoma model was constructed as follows: after the mice were anesthetized with mixed anesthesia, 2 μl (concentration of approximately 5.0×10 6MB / ml) microbeads with a diameter of 15 μm (Invitrogen) were injected into the anterior chamber. IOP was measured using Icare TonoLab (Icare, Finland) on days 1, 3, 7, 14, 21, and 28 after surgery.

[0051] 2) Indoleacetic acid intervention

[0052] Indoleacetic acid powder was dissolved in DMSO to 100 mg / mL. On the day of establishing the glaucoma mouse model, indoleacetic acid (20 mg / kg body weight) was intraperitoneally injected and then administered once a day.

[0053] 3) Histological and morphological analysis

[0054] Retinal flat mounts or eye sections were prepared 14 or 28 days after glaucoma modeling for histological and morphological analysis. For sampling, the mouse eye was perfused with normal saline and 4% paraformaldehyde. After perfusion, the eye was removed and placed in FAS eye fixative (Servicebio) overnight. For flat mounts, the mouse retina was completely removed, flattened, and fixed in 4% paraformaldehyde for 15 minutes. The retina was then blocked for 1 hour with 5% goat serum and 0.3% Triton-X100 in PBST. The retina was incubated with the primary antibody against β-III tubulin (1:1000, Abcam) in a humidified chamber overnight at 4°C, followed by incubation with the secondary antibody conjugated with Alexa Fluor 594 (1:200, Abbkine) for 2 hours. Images were captured using a fluorescence confocal microscope (Nikon). Eight fields of view were selected from the central and peripheral retina, and β-III tubulin-positive cells were counted using ImageJ. For eye sections, OCT-embedded sections were frozen and sliced ​​(10 μm) using a cryostat. Retinal structure was analyzed by hematoxylin-eosin staining. The number of retinal ganglion cell layer (GCL) cells, retinal nerve fiber layer (RNFL) thickness, and inner plexiform layer (IPL) thickness were counted in five consecutive fields of view for each section. The average values ​​were calculated and normalized to the control group.

[0055] 4) Mouse visual function testing

[0056] A visual cliff test was used to assess the visual function of mice. The experimental apparatus consisted of a transparent glass box (60 cm long, 60 cm wide, and 15 cm high). Half of the box was suspended over the edge of a test bench, forming the "cliff" side (90 cm above the ground); the other half remained on the test bench, forming the "platform" side. A transparent platform (10 × 7 cm, 2 cm high) was placed in the center of the box. Both the test bench and the floor were covered with an alternating black and white pattern (2 cm long) to aid the mice's depth perception. Light sources were placed 30 cm above and 30 cm below the test area to illuminate the test area. At the start of the experiment, mice were placed on the transparent platform. The direction the mice first chose (cliff or platform) and the number of mice that first stepped onto the cliff were recorded. Furthermore, the total time each mouse spent in the "cliff" area during the first two minutes was recorded. Each mouse was tested only once, and the platform and box were thoroughly cleaned after each experiment.

[0057] 5) Retinal immunofluorescence

[0058] Mouse retinal sections were prepared according to the above procedure and lysed with 0.3% Triton X-100 for 15 minutes at room temperature. The sections were then blocked for 1.5 hours with PBS containing 5% goat serum (Boster) and 0.3% Triton X-100. The sections were incubated overnight at 4°C in a humidified chamber with primary antibodies against TNFα (1:200, Proteintech), IL-1β (1:200, Proteintech), IL-6 (1:200, Proteintech), iNOS (1:200, Abclonal), RAGE (1:200, Abmart), and Iba1 (1:100, Servicebio, Wuhan). The sections were then incubated with secondary antibodies against Alexa Fluor 488 rabbit or Alexa Fluor 594 mouse (1:200, Abbkine) for 1 hour at room temperature. Cell nuclei were stained with DAPI (Invitrogen). Finally, images were captured using a confocal microscope (Nikon). At least three samples were included in each group. To assess microglial activation, five randomly selected fields of view were obtained from each retina. The number of Iba1-positive cells and the accumulated optical density (IOD) were counted and averaged; each group included six samples. The results were analyzed using ImageJ software and normalized to the control group.

[0059] 6) RNA extraction and real-time quantitative PCR (qPCR)

[0060] Total RNA from retinal tissue was extracted using TRIzol reagent. RNA concentration and purity were determined using Nanodrop (THERMOFISHER), and reverse transcription was performed using the PrimeScript RT Reverse Transcription Kit (Takara). Primers used in this study were referenced from PrimerBank and synthesized by Qingke Biotechnology (Beijing). For gene expression analysis, β-actin was used as an internal reference, and expression fold changes were calculated using the 2^-Δ (ΔCT) relative quantification method.

[0061] 7) Western blot

[0062] Total protein from retinal tissue was extracted using RIPA lysis buffer (Sanger Biotechnology). Protein samples were separated by electrophoresis on 10% SDS-PAGE gels and transferred to polyvinylidene fluoride (PVDF) membranes. The membranes were then blocked with 5% nonfat dry milk in Tris-buffered saline containing Tween-20. The membranes were incubated overnight at 4°C with the following primary antibodies: TNFα (1:1000, Proteintech), IL-1β (1:1000, Proteintech), IL-6 (1:1000, Proteintech), iNOS (1:1000, Abclonal, Wuhan, China), NFκB (1:1000, Proteintech), and p-NFκB (1:1000, Abcam), followed by incubation with anti-rabbit or anti-mouse secondary antibodies (1:1000, Beyotime) for 1 hour at room temperature. The membrane was developed using a Tanon imaging system (Shanghai) and BeyoECL Moon developer (Beyotime), and the images were quantitatively analyzed using ImageJ software.

[0063] 8) Statistical methods

[0064] Data are expressed as mean ± standard deviation, and statistical analysis was performed using GraphPad Prism 8.0 software. Comparisons between two groups were analyzed using the t-test. When the number of groups was greater than two, one-way analysis of variance followed by Turkey's test was used. A P value of < 0.05 was considered statistically significant.

[0065] Example 1

[0066] This example verifies the effect of indoleacetic acid on alleviating retinal damage and retinal ganglion cell loss in glaucoma model mice.

[0067] Retinal flat mounts, immunofluorescence staining and confocal microscopy were performed on mice in each group. Typical visual fields are shown in the figure below. Figure 1 As shown in a. The β-III tubulin positive cells in each field of view were counted and statistically analyzed ( Figure 1bc), compared with the control group (Control, white), the percentage of retinal ganglion cells in glaucoma model mice (MB, blue) was significantly decreased, while the percentage of retinal ganglion cells was significantly increased after administration of indoleacetic acid (MB+IAA, red).

[0068] Eyeball sections and retinal hematoxylin-eosin staining were performed on mice in each group. Typical visual fields are shown in Figure 2. Figure 2 As shown in a. The cell density of the retinal ganglion cell layer (GCL), the thickness of the retinal nerve fiber layer (RNFL), and the thickness of the inner plexiform layer (IPL) of each group of mice were statistically analyzed. It can be seen that the GCL cell density and RNFL thickness of the glaucoma model mice (MB, blue) were significantly reduced, while after intraperitoneal injection of indoleacetic acid (MB+IAA, red), the GCL cell density and RNFL thickness were significantly increased ( Figure 2 b–d).

[0069] The above results indicate that indoleacetic acid can maintain the number of retinal ganglion cells and the thickness of the retinal nerve fiber layer, proving that it can alleviate retinal damage and retinal ganglion cell loss.

[0070] Example 2

[0071] This example verifies the effect of indoleacetic acid on visual function indicators in a visual cliff test in glaucoma model mice.

[0072] The test showed that compared with the control group (Control), the number of mice that first stepped onto the cliff side (blue part) in the glaucoma model mice (MB) increased, and the total time they stayed on the cliff side (blue part) was significantly increased. The visual function of the glaucoma mice treated with indoleacetic acid (MB+IAA) was protected, as shown by a decrease in the number of mice that first stepped onto the cliff side ( Figure 3 a) and shortened time spent on the cliff side ( Figure 3 b).

[0073] These results indicate that indoleacetic acid effectively improves the visual function of glaucoma model mice.

[0074] Example 3

[0075] This example verifies the effect of indoleacetic acid on inhibiting the activation of retinal microglia in glaucoma model mice.

[0076] To evaluate the effect of indoleacetic acid on the activation of retinal microglia in glaucoma model mice, we used Iba1 primary antibody (1:100, Servicebio) and Alexa Fluor 488 anti-rabbit secondary antibody to perform immunofluorescence staining on mouse retinal flat mounts. Typical fields of view under confocal microscopy are shown in Figure 2. Figure 4As shown in a. Compared with the control group, glaucoma model mice (MB, blue) showed a higher number of Iba1-positive cells and Iba1 cumulative optical density (IOD), while indoleacetic acid supplementation significantly reduced the number of Iba1-positive cells and Iba1 cumulative optical density (IOD). Figure 4 b–c).

[0077] The above results indicate that indoleacetic acid can inhibit the activation of retinal microglia in glaucoma model mice.

[0078] Example 4

[0079] This example verifies the effect of indoleacetic acid on inhibiting the activation of retinal inflammatory pathways and the expression of inflammatory mediators in glaucoma model mice.

[0080] This example uses real-time quantitative PCR, Western blotting, and immunofluorescence to detect changes in the expression of key proteins and inflammatory mediators in the retinal inflammatory pathway of glaucoma model mice. Compared with the control group, the expression of iNOS and the ratio of phosphorylated NFκB / NFκB in glaucoma model mice (MB) were significantly higher than those in the control group (Control). Supplementation with indoleacetic acid (MB+IAA) significantly alleviated their expression ( Figure 5 ac). Compared with the control group, the expression of TNF-α, IL-1β and IL-6 in glaucoma model mice (MB) was significantly higher at the protein level ( Figure 5 d–g) and mRNA levels ( Figure 5 h) were all upregulated, and the immunofluorescence quantitative results further verified this ( Figure 5 i), while supplementation of indoleacetic acid significantly inhibited the expression of the above inflammatory factors ( Figure 5 d–i).

[0081] The above experimental results show that indoleacetic acid can inhibit the activation of retinal inflammatory pathways and the expression of inflammatory mediators in glaucoma model mice.

[0082] The above results indicate that indoleacetic acid can be used as a drug for protecting the optic nerve in glaucoma and for the treatment of glaucoma or optic nerve damage.

Claims

1. Use of the compound indoleacetic acid in the preparation of medicines or foods for treating glaucoma.

2. The use according to claim 1, characterized in that The compound indoleacetic acid can reduce optic nerve damage caused by glaucoma and protect visual function.

3. The use according to claim 1, characterized in that The compound indoleacetic acid can maintain the number of retinal ganglion cells and the thickness of the retinal nerve fiber layer.

4. The use according to claim 1, characterized in that The compound indoleacetic acid can inhibit the activation of retinal microglia.

5. The use according to claim 1, characterized in that Inhibit the activation of retinal inflammatory pathways and the expression of inflammatory mediators.

6. The use according to claim 1, characterized in that The indoleacetic acid is produced by a bioreactor.

7. The use according to claim 6, characterized in that The bioreactor includes exogenous genetic material and is regulated to produce indoleacetic acid.

8. The use according to claim 7, characterized in that The exogenous genetic material is the indoleacetic acid producing gene of Bacteroides fragilis.

9. The use according to claim 6, characterized in that The bioreactor is Bacteroides fragilis.

10. A medical device, characterized in that The invention comprises the indoleacetic acid according to claim 1.

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