Application of TASK-3 agonist or TASK-3 overexpression biological product in preparation of medicine for restoring visual function and preventing and / or treating optic nerve injury

Abstract

The invention belongs to the technical field of medicines, and particularly relates to application of a TASK-3 agonist or a TASK-3 overexpression biological product in preparation of a medicine for recovering a visual function and preventing and / or treating optic nerve injury. The TASK-3 selective agonist CHET3 disclosed by the invention can be used for inhibiting retinal ganglion cell injury induced by optic nerve extrusion, protecting the quantity of retinal ganglion cells and saving the visual function after injury. The invention also finds that the visual function of the optic nerve extrusion mouse can be recovered by specific overexpression of TASK-3 in the retinal ganglion cells. The invention provides a new treatment strategy for clinically improving the eyesight of a patient and delaying the disease progress, and has a wide application prospect in medical research and clinical practice of optic nerve injury.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and specifically relates to the use of a TASK-3 agonist or a biological product overexpressing TASK-3 in the preparation of a drug for restoring visual function, preventing and / or treating optic nerve damage. Background Art

[0002] Retinal ganglion cells (RGCs) are located in the innermost layer of the retina. Their axons converge into bundles to form the optic nerve, which transmits visual signals to the brain. Currently, a large number of studies have been conducted on the mechanisms related to RGC damage, including the nutritional factor theory and the excitotoxic damage theory. Excitotoxic damage is based on the excessive binding of glutamate to ionized glutamate receptors (such as NMDA receptors), which triggers calcium (Ca) 2+ ) influx, organelle stress, and cell apoptosis. Excessive intracellular Ca 2+ Excites RGCs, produces a variety of cytotoxic substances, destroys cell structure, causes RGC apoptosis, and impairs visual function.

[0003] Traumatic optic neuropathy (TON) is a pathological condition caused by direct or indirect damage to the optic nerve, typically resulting in partial or permanent visual impairment due to the massive loss of retinal ganglion cells and their axonal fibers. The optic nerve crush (ONC) model can simulate this pathological injury. In the rodent ONC injury model, retinal microglia are gradually activated and phagocytose damaged cells. However, due to the extremely low phagocytic capacity of retinal microglia, growth-inhibitory myelin debris and glial scars formed by reactive astrocytes inhibit the regeneration of RGC axons, which contributes to the poor recovery of visual function in patients with TON.

[0004] Studies have shown that activating the CaMKII pathway through gene editing can protect RGCs from excitotoxicity and optic nerve damage. However, currently, there are limited drugs that effectively protect against optic nerve damage. Therefore, the development of drugs to prevent and treat optic nerve damage is of great research value.

[0005] The two-pore domain acid-sensitive potassium channel (TASK) is an important member of the two-pore domain potassium channel (K2P channel) family of channels, including TASK-1, TASK-3, and TASK-5. It can generate acid-sensitive background potassium currents and can regulate cell membrane potential through various stimuli, such as mechanical force, arachidonic acid, and pH changes. TASK-3 is expressed in both the central and peripheral nervous systems. Recent studies have found that TASK-3 channels can be used as peripheral analgesic targets. In the retina, TASK-3 is distributed in almost all retinal ganglion cells (RGCs) (Xiangyi Wen et al., Tandem pore domain acid-sensitive K channel 3 (TASK-3) regulates visual sensitivity in healthy and aging retina. Sci. Adv. 8, eabn8785 (2022).). However, there are no reports of treating optic nerve damage by activating TASK-3. Summary of the Invention

[0006] In order to solve the above problems existing in the prior art, the object of the present invention is to provide a use of a TASK-3 agonist or a biological product overexpressing TASK-3 in the preparation of a drug for restoring visual function, preventing and / or treating optic nerve damage.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions:

[0008] The present invention provides use of a TASK-3 agonist or a biological product overexpressing TASK-3 in the preparation of a medicament for restoring visual function, preventing and / or treating optic nerve damage.

[0009] Furthermore, the optic nerve damage is traumatic optic neuropathy or retinal ganglion cell damage.

[0010] Furthermore, the optic nerve damage is traumatic optic neuropathy.

[0011] Furthermore, the TASK-3 agonist is a small molecule compound, polypeptide or antibody that can activate TASK-3.

[0012] Furthermore, the small molecule compound capable of activating TASK-3 is CHET3 or NPBA.

[0013] Furthermore, the biological products that overexpress TASK-3 include drugs for T cell-directed overexpression, drugs for adeno-associated virus-mediated overexpression, drugs for lentivirus-mediated overexpression, drugs for adenovirus-mediated overexpression, drugs for retrovirus-mediated overexpression, drugs for regulating enhancer-induced overexpression, drugs for regulating transcription-induced overexpression, drugs for regulating transcription element-induced overexpression, small molecule drug response systems for overexpressing genes, Cre-loxp system, Flp-frt system, and Dre-rox system.

[0014] Furthermore, the biological product overexpressing TASK-3 includes a drug overexpressed by adeno-associated virus, and the adeno-associated virus is AAV2.

[0015] Furthermore, the adeno-associated virus contains the RGC-specific promoter Ple345 (NEFL) and the TASK-3 gene.

[0016] Furthermore, the medicine is an external preparation.

[0017] Furthermore, the external preparation is an ophthalmic gel.

[0018] Furthermore, the ophthalmic gel is prepared using a cosolvent, a stabilizer and a TASK-3 agonist as raw materials; the mass ratio of the cosolvent to the stabilizer is 0.1 to 5:1, and the final concentration of the TASK-3 agonist is 0.1 to 5 mg / ml.

[0019] Furthermore, the mass ratio of the cosolvent to the stabilizer is 1.2:1, and the final concentration of the TASK-3 agonist is 0.7 mg / ml.

[0020] Furthermore, the co-solvent is at least one of cyclodextrin and dimethyl sulfoxide, the stabilizer is at least one of poloxamer, polysorbate, and polyethylene glycol, and the TASK-3 agonist is at least one of CHET3 and NPBA; preferably, the co-solvent is cyclodextrin, the stabilizer is poloxamer, and the TASK-3 agonist is CHET3.

[0021] The present invention has achieved the following beneficial effects:

[0022] The TASK-3 selective agonist CHET3 of the present invention can inhibit retinal ganglion cell (RGC) damage induced by optic nerve crush (ONC), protect RGC number, and rescue visual function after injury. The present invention also found that overexpressing TASK-3 specifically in RGCs can restore visual function in ONC mice. This invention provides a new therapeutic strategy for improving patient vision and delaying disease progression in clinical practice, and has broad application prospects in medical research and clinical practice of optic nerve injury.

[0023] Obviously, based on the above contents of the present invention, according to common technical knowledge and customary means in this field, without departing from the above basic technical ideas of the present invention, other various forms of modifications, replacements or changes can be made.

[0024] The following further describes the above content of the present invention in detail through specific embodiments in the form of examples. However, this should not be construed as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above content of the present invention fall within the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 Activation of TASK-3 protects RGCs from ONC injury. (A) Confocal image of a retinal flat-mount from the ONC group shows RGCs labeled with RBPMS. (B) Confocal image of a retinal flat-mount from the sham-operated (SHAM) group shows RGCs labeled with RBPMS. (C) RGC counts in the ONC and SHAM groups (n = 5-6). (D) Description of the channel strategy for activating TASK-3. (E) Confocal image of a retinal flat-mount shows RGCs labeled with RBPMS in an ONC eye treated with CHET3. (F) Confocal image of a retinal flat-mount shows RGCs labeled with RBPMS in an ONC eye treated with DMSO. (G) to (I) RGC counts were performed in the whole, central, and peripheral retinas of CHET3- and DMSO-treated ONC eyes (n = 12 retinas per group, unpaired t-test). All data are presented as mean ± SEM. *P < 0.05.

[0026] Figure 2 To protect visual function, activation of TASK-3 was performed. (A) Example visual evoked potential (VEP) waveforms after administration of CHET3 or vehicle DMSO to the ONC eye. (B) Histogram of VEP amplitudes in the ONC eye after administration of CHET3 or vehicle DMSO (n = 14 to 17, unpaired t-test). (C) Schematic diagram of the visual cliff test. (D) Histogram of the discrimination index of the visual cliff test in mice after administration of CHET3 or vehicle DMSO to the ONC eye (n = 12, unpaired t-test). (E) Schematic diagram of the visual water maze test. (F) to (G) Histograms of visual spatial frequency (n = 14 to 16, unpaired t-test) and contrast sensitivity (n = 26, unpaired t-test) in the visual water maze test after administration of CHET3 or vehicle DMSO to the ONC eye. All data are expressed as mean ± SEM. *P < 0.05; **P < 0.01; ****P < 0.0001.

[0027] Figure 3Overexpression of Kcnk9 specifically in retinal ganglion cells (RGCs) restores visual function in ONC mice. (A) Viral injection strategy for overexpressing TASK-3. (B) to (D) RNAscope in situ hybridization showing overexpression of control and TASK-3 viruses in sham-operated (SHAM) and ONC mice. (E) Bar graph of Kcnk9 mRNA expression levels (n = 10 to 11, unpaired t-test). (F) to (G) Bar graphs of visual spatial frequency (n = 26, unpaired t-test) and contrast sensitivity (n = 26, unpaired t-test) in overexpression and control mice tested using a visual water maze. All data are presented as mean ± SEM. *P < 0.05; ***P < 0.001. DETAILED DESCRIPTION

[0028] The reagents and equipment used in the specific embodiments of the present invention are all known products and are obtained by purchasing commercial products.

[0029] The mice used in the present invention are all C57BL / 6 mice.

[0030] The preparation method of CHET3 ophthalmic gel is as follows:

[0031] 1. Preparation of gel: Add 0.3 g of β-cyclodextrin powder (Shanghai Yuanye Biotechnology Co., Ltd., S11013-100G) as a cosolvent to 1 ml of normal saline, mix well, then add 0.25 g of gel (Poloxamer 407) powder and place at 4°C until it is fully dissolved into a transparent gel.

[0032] 2. Prepare CHET3 stock solution: Dissolve 0.7 mg CHET3 in 70 μl DMSO and store at -20°C. When needed, mix the gel with the CHET3 stock solution to achieve a final CHET3 concentration of 0.7 mg / ml in the CHET3 ophthalmic gel.

[0033] Example 1: Activation of TASK-3 protects RGCs from ONC damage

[0034] (1) Experimental methods

[0035] Construction of the optic nerve crush model:

[0036] The procedure simulates injury caused by compression of the optic nerve, which results in the death of retinal ganglion cells.

[0037] Before surgery, mice were intraperitoneally injected with anesthetic (tribromoethanol, 40 mg / ml, St. Louis, MO, USA), and the left eye was selected as the model eye. The mouse was placed under a dissecting microscope so that the operator could accurately visualize the conjunctiva. A small incision was made in the conjunctiva at approximately 4 o'clock with microscissors, and the surrounding tissue and venous sinus of the optic nerve were carefully bluntly separated with microtweezers. The yellow-white optic nerve was exposed, and a compression injury was applied to the optic nerve at a distance of about 2 mm from the eyeball for about 5 seconds, taking care not to damage the venous sinus around the eyeball. After surgery, the mouse was placed on a heating pad until recovery and returned to the cage to obtain an optic nerve compression model mouse.

[0038] (2) Experimental results

[0039] The left eyes of 7-week-old C57BL / 6 mice underwent optic nerve crush (ONC) surgery and were immediately treated with an ophthalmic gel containing the TASK-3 specific agonist CHET3. A control group received an ophthalmic gel containing only DMSO.

[0040] The results are as follows Figure 1 As shown, after ONC surgery, daily application of CHET3 for one week reduced the number of RGCs by approximately 40% compared to uninjured eyes. In the control group (i.e., the vehicle solution DMSO, β-cyclodextrin, and poloxamer in equal proportions), the number of RGCs decreased by approximately 35%. Counting the number of RGCs in the peripheral and central retina of mice treated with CHET3 revealed that the number of RGCs in the central and peripheral retina of mice treated with CHET3 was 5% higher than that in the blank control group.

[0041] This experiment demonstrated that activation of TASK-3 has a protective effect on the number of retinal ganglion cells after optic nerve crush-induced retinal ganglion cell injury.

[0042] Example 2: TASK-3 activation protects visual function

[0043] (1) Experimental methods

[0044] (1) Skull pin implantation

[0045] The surgery was designed to ensure the consistency of flash-visual evoked potential (VEP). Mice were intraperitoneally injected with anesthetic (tribromoethanol, 40 mg / ml) before surgery. Hair around the bregma was removed from the scalp, and the exposed skin was disinfected with povidone-iodine (Chengdu Yongan Pharmaceutical Co., Ltd.). Microsurgery scissors were then used to remove the exposed skin, exposing the skull, and the pericranium was carefully removed with microsurgical forceps. Under a microscope, a micro-skull drill (Shenzhen Ruiwode Life Science Co., Ltd., 78001 Micro Handheld Skull Drill) was used to drill a hole in the designated skull area to a depth of approximately 400 μm. A stainless steel flat-head screw (M0.8x4 mm) was then placed in the skull hole, making slight contact with the cortex. A reference electrode was placed on the right prefrontal cortex (2.0 mm anterior to bregma), and a recording electrode was placed on the right primary visual cortex (3.6 mm caudal to bregma and 2.3 mm lateral to bregma). Dental cement (glass ionomer cement, Changshu Shangchi Dental Materials Co., Ltd.) was used to fix the skull screws and seal the exposed skull area. After surgery, the mice were kept warm on a heating pad until they woke up.

[0046] (2) Flash-VEP detection

[0047] After installing the skull pins as described above, coils of silver wire were placed over the reference and recording electrodes and connected to each electrode using conductive alligator clips. A ground electrode was clipped to the mouse's tail. White flashes were used as stimuli with a stimulation frequency of 1.0 Hz, a bandpass of 0.5-85.0 Hz, a sampling frequency of 2000 Hz, an analysis time of 500 ms, and 100 superpositions. When testing one eye, completely cover the other eye with an opaque black eyepatch. The left and right eyes were tested sequentially.

[0048] (3) Visual cliff behavioral experiment

[0049] The visual cliff behavioral experiment is used to assess stereopsis in mice. The experimental apparatus consists of two custom-made transparent rectangular acrylic boxes. The lower box measures 84 x 53 x 41 cm, and the upper box measures 84 x 53 x 50 cm. The two acrylic boxes overlap and are covered with black paper on all four sides to reduce reflections. The left side (deep layer) of the lower box is covered with a black and white checkered pattern (3.0 x 3.0 cm). The right side (shallow layer) of the upper box also has the same black and white checkered pattern, while the left side (shallow layer) is covered with a transparent acrylic sheet. Mice can move freely on either side of the upper box. The black and white checkered pattern of varying heights can induce a depth illusion in normal mice. During the experiment, mice are released from the center of the upper box, and the time they spend on either side is recorded with a camera over a 5-minute period. The discrimination index (DI), which is (time spent in the shallow checkered area minus time spent in the deep checkered area) divided by total time, can be used to assess stereopsis. Normal mice spend the majority of their time in the shallow checkered area. If the mouse's stereoscopic vision is impaired, it cannot produce the illusion of depth, and the mouse will have no preference for the activity area. After each experiment, clean the box with low-concentration alcohol and keep it dry.

[0050] (4) Visual water maze experiment

[0051] The visual water maze test is used to assess the visual acuity and contrast sensitivity of mice. The water maze apparatus consists of an isosceles trapezoidal pool composed of acrylic panels, painted black to reduce glare. Two computer monitors are placed parallel to each other at the long end of the pool. A black-painted pool divider, 40 cm high and 46 cm long, is located between the two monitors. The divider divides them into two choice channels. A transparent escape platform is placed at the bottom in front of the monitors, invisible when the water surface just covers the platform. After being released from the other side of the pool, mice are required to make a choice in front of the divider. This can be used to train mice to escape from the water surface to the escape platform under the display fence. The test consists of a training phase, a maintenance phase, and a test phase.

[0052] During the training phase, mice were first placed on a survival platform beneath a display fence, allowing them to perceive the platform in the water. They were then released from near and far positions, forcing them to swim toward the survival platform. Finally, they were released from a release channel on the other side of the pool, forcing them to swim to the platform beneath the screen with the grating. The training phase lasted three to five days, with mice trained two to four times daily, eight to ten times per round, at a 0.12 cpd (cycle per degree) grating frequency and 100% contrast. Training was considered complete when the mice achieved an 80% accuracy rate for two consecutive rounds.

[0053] The maintenance training period refers to the training of mice that have learned before the formal test. During this period, their accuracy may fluctuate, but it is necessary to ensure that the accuracy reaches 80% in at least two of the three rounds of training before the formal test.

[0054] The testing phase, which included spatial frequency and contrast sensitivity testing, lasted two to three days. The test phase began at 0.12 cpd, and the mouse progressed to the next grating frequency after five consecutive correct choices. The grating frequency gradient increased by 0.06 cpd each time. After each correct choice, the mouse progressed to the next grating frequency. If the choice was incorrect, the mouse repeated the test at that grating frequency 8 to 15 times. If the final accuracy at that grating frequency was 70% or above, the mouse continued to test the next spatial frequency until the accuracy fell below 70%. A line graph of spatial frequency accuracy was plotted to determine the grating frequency corresponding to the 70% accuracy threshold.

[0055] Contrast sensitivity testing was similar to the above. The grating frequency was maintained at 0.12 cpd, and the initial contrast sensitivity was 100%. Contrast sensitivity was then decreased in 10% increments, with each correct choice followed by a decrease in contrast sensitivity. After each correct choice, the mouse progressed to the next contrast sensitivity. If an incorrect choice was made, the test was repeated 8 to 15 times at that contrast. If the final accuracy at that contrast was 70% or above, the mouse continued testing the next spatial frequency until the accuracy fell below 70%. A line graph of contrast sensitivity accuracy was plotted to obtain the contrast sensitivity corresponding to the 70% accuracy threshold.

[0056] (2) Experimental results

[0057] The RGC activity in response to flash visual stimulation was measured by flash visual evoked potential (f-VEP). Figure 2 As shown in A-2B, application of CHET3 after ONC resulted in more pronounced bimodal P waves and higher P wave amplitude (38.4 uV) compared with the control group (DMSO, 27.6 uV), indicating that activation of TASK-3 can protect the function of the entire visual pathway from the retina to the primary visual cortex of the brain.

[0058] Stereoscopic vision was assessed by visual cliff behavioral experiments. Figure 2 As shown in C-2D, in the ONC + CHET3 group, DI was significantly higher than that in the ONC + DMSO group, and most mice in the CHET3-treated group stayed on the shallow side longer during the test.

[0059] A visual water maze was used to determine whether activation of TASK-3 could protect visual acuity and contrast sensitivity. Figure 2 As shown in E-2G, compared with the control group (DMSO), the binocular vision of ONC mice carrying CHET3 was significantly improved, while the sensitivity of the control group was significantly reduced.

[0060] This study demonstrated that specific activation of TASK-3 in retinal ganglion cells of mice with optic nerve crush injury can protect them from visual function damage.

[0061] Example 3: Specific overexpression of TASK-3 in RGCs

[0062] (1) Experimental methods

[0063] To specifically overexpress TASK-3 in RGCs, the present invention synthesized the coding sequence of the RGC-specific promoter Ple345 (NEFL) (pEMS2280; catalog number 111901, Addgene, Watertown, MA, USA) and the mouse TASK-3 gene (Kcnk9; NCBI, gene identifier: 223604) and cloned them into AAV2. The overexpression virus [AAV2-Ple345 (NEFL)-kcnk9-HAx2-Flag] (abbreviation of AAV2-TASK-3) was prepared by fusion with two tandem copies of HA and Flag tags (catalog number AAV2 / 2-WY3239, Taitool Bioscience, Shanghai, China). The control virus encodes EGFP with a Flag tag and the same promoter [AAV2-Ple345 (NEFL)-EGFP-3Flag] (AAV2-control) (product number S0837-2-H50, Taitool Bioscience). The virus was injected intravitreally into the eyes of ONC mice (0.5 × 10 10 Three weeks later, the animals were euthanized and their retinas harvested for immunohistochemistry and in situ RNA hybridization as described below.

[0064] (1) Immunofluorescence staining

[0065] After ONC mice were sacrificed by cervical dislocation, the eyeballs were enucleated and placed in a glass dish containing PBS solution. Under a microscope, a hole was punctured in the cornea with a blade. The cornea was carefully excised along the hole using microscissors. The sclera was carefully torn open along the edge of the sclera using microtweezers, the optic nerve was severed, the lens was removed, and the retina was completely isolated. The isolated retina was transferred to a filter paper sheet (nitrocellulose membrane, 0.8 mm pores, Millipore) using a glass pipette. The retina was cut into a "four-leaf clover" shape using microscissors and laid flat on the filter paper. Excess PBS solution was removed with absorbent paper, and PBS was then dripped and blotted dry three times to ensure that the retina adhered tightly to the filter paper sheet. The retinal patch was transferred to a 48-well plate, and 250 μl of 4% paraformaldehyde (PFA) was added to each well and fixed at room temperature for 30 minutes. After fixation, the 4% PFA was removed and the cells were carefully washed three times with PBS solution for 5 minutes each. Fixed retinal patches were blocked in PBS containing 5% normal goat serum (NGS) and 0.5% Triton for 60 minutes at room temperature. Patches were then incubated with a rabbit antibody against RNA binding protein with multiple splicing (RBPMS) (1:1000; catalog no. ab152101, Abcam, Cambridge, UK) at 4°C overnight. Patches were washed again in PBS three times for 20 minutes each. Patches were then incubated with Alexa Fluor 488 goat anti-rabbit (1:1000; catalog no. 111-605-003, Jackson ImmunoResearch Laboratories, West Grove, PA, USA) secondary antibody for 2 hours at room temperature. Retinal patches were washed again three times for 20 minutes each. Finally, the patches were transferred to glass slides, and excess PBS was removed with absorbent paper. Finally, the mount was mounted with a mounting medium containing 4′,6-diamidino-2-phenylindole (DAPI) (DAPI Fluoromount-G, catalog no. 0100-20, Southern Biotech, Birmingham, AL, USA).

[0066] (2) In situ RNA hybridization

[0067] After ONC mice were sacrificed by cervical dislocation, the eyeballs were enucleated and placed in a glass dish containing PBS. Under a microscope, a hole was punctured in the cornea with a razor blade and fixed in 4% paraformaldehyde (PFA) overnight at 4°C. The eyes were washed three times with PBS for 5 minutes each and then dehydrated in 30% sucrose solution at 4°C for 1 day. The dehydrated eyeballs were placed in cassettes containing OCT (Optimal Cutting Temperature Compound) embedding medium, snap-frozen at -80°C, and 15-μm-thick cryosections were prepared using a cryostat. RNA in situ hybridization was performed using the RNAscope Multiplex Fluorescent Reagent Kit v2 (catalog no. 323100, Advanced Cell Diagnostics, Newark, CA, USA) and the RNAscope 4-Plex Ancillary Kit (catalog no. 323120) according to the manufacturer's instructions. A probe targeting Kcnk9 (catalog no. 475681) was used. Images were captured using an A1R+MP two-photon confocal scanning microscope (Nikon, Tokyo, Japan).

[0068] (2) Experimental results

[0069] Specific overexpression of Kcnk9 in RGCs restored visual function in ONC mice.

[0070] TASK-3 mRNA levels were quantified by measuring the fluorescence level in the retina of ONC mice using in situ hybridization (RNAscope). In this experiment, 7-week-old C57BL / 6 mice underwent ONC surgery. One week after the mice had a significant decrease in vision, the overexpressing virus was injected into the vitreous of the crushed eyes (0.5×10 per eye). 10 Three weeks later, visual function was assessed using a visual water maze test and a visual cliff behavioral test, and retinal tissues were collected for in situ RNA hybridization.

[0071] The results are as follows Figure 3 As shown, overexpression of TASK-3 (AAV2-TASK-3) specifically in RGCs of ONC mice significantly increased TASK-3 mRNA expression. TASK-3 overexpression restored the decreased visual acuity (spatial frequency) and contrast sensitivity induced by ONC injury.

[0072] This experiment demonstrated that specific overexpression of TASK-3 could restore the decreased visual acuity and contrast sensitivity caused by optic nerve crush injury.

[0073] In summary, the TASK-3 selective agonist CHET3 of the present invention can inhibit retinal ganglion cell (RGC) damage induced by optic nerve crush (ONC), protect RGC number, and rescue visual function after injury. The present invention also found that overexpressing TASK-3 specifically in RGCs can restore visual function in ONC mice. This invention provides a new therapeutic strategy for improving patient vision and delaying disease progression in clinical practice, and has broad application prospects in medical research and clinical practice of optic nerve injury.

Claims

1. Use of a TASK-3 agonist or a biological product that overexpresses TASK-3 in the preparation of a drug for restoring visual function, preventing and / or treating optic nerve damage.

2. The use according to claim 1, characterized in that: The optic nerve damage is traumatic optic neuropathy or retinal ganglion cell damage; preferably, it is traumatic optic neuropathy.

3. The use according to claim 1, characterized in that: The TASK-3 agonist is a small molecule compound, polypeptide or antibody that can activate TASK-3.

4. The use according to claim 3, characterized in that: The small molecule compound capable of activating TASK-3 is CHET3 or NPBA.

5. The use according to claim 1, characterized in that: The biological products that overexpress TASK-3 include drugs for T cell-directed overexpression, drugs for adeno-associated virus-mediated overexpression, drugs for lentivirus-mediated overexpression, drugs for adenovirus-mediated overexpression, drugs for retrovirus-mediated overexpression, drugs for regulating enhancer-induced overexpression, drugs for regulating transcription-induced overexpression, drugs for regulating transcription element-induced overexpression, small molecule drug response systems for overexpressing genes, Cre-loxp systems, Flp-frt systems, and Dre-rox systems.

6. The use according to claim 5, characterized in that: The biological product overexpressing TASK-3 includes a drug overexpressed by adeno-associated virus, wherein the adeno-associated virus is AAV2.

7. The use according to claim 6, characterized in that: The adeno-associated virus contains the RGC-specific promoter Ple345 (NEFL) and the TASK-3 gene.

8. The use according to claim 1, characterized in that: The medicine is an external preparation.

9. The use according to claim 8, characterized in that: The external preparation is an ophthalmic gel.

10. The use according to claim 9, characterized in that: The ophthalmic gel is prepared using a cosolvent, a stabilizer and a TASK-3 agonist as raw materials; the mass ratio of the cosolvent to the stabilizer is 0.1 to 5:1, and the final concentration of the TASK-3 agonist is 0.1 to 5 mg / ml.

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