Application of prostaglandin D2 in preparation of medicine for treating optic neuropathy

Abstract

The invention discloses an application of prostaglandin D2 in preparation of a medicine for treating optic neuropathy. The optic neuropathy is optic nerve injury caused by traumatic optic neuropathy. Animal experiments find for the first time that intravitreal injection of prostaglandin D2 can significantly improve optic ganglion cell survival and optic nerve axon regeneration and repair, and the prostaglandin D2 is safe and reliable.

Description

Technical Field:

[0001] The present invention relates to the field of biomedical technology, and particularly to the application of prostaglandin D2 in the preparation of drugs for treating optic nerve diseases. Background Art:

[0002] Prostaglandin (PG) is a bioactive lipid synthesized through the cyclooxygenase COX pathway. Through the action of different downstream prostaglandin synthases, it can be further metabolized into various different types of prostaglandins, including PGI2, PGE2, PGF2, and prostaglandin D2 (PGD2), etc. It plays an important role in inflammation, immune response, and various cell biological processes through autocrine or paracrine methods, and has been found to be closely related to the development of various diseases such as atherosclerosis, thrombotic diseases, and hypertension.

[0003] Prostaglandin D2 (PGD2) is mainly produced in the central nervous system and immune system. Existing studies have found that it plays an important role in sleep regulation and immune response. Therefore, as a bioactive component, the safety of PGD2 in drug treatment is controllable.

[0004] Excessive apoptosis of retinal ganglion cells (RGCs) caused by optic nerve axon injury and degeneration is a common pathological feature of neurodegenerative diseases such as traumatic optic neuropathy and glaucoma, leading to irreversible loss of vision and seriously threatening human visual health. Although hormone and neurotrophic drug treatment or optic nerve canal decompression surgery have been applied in clinical routine treatment, the curative effect is not very ideal. How to avoid visual function damage after optic nerve injury and promote the regeneration and repair of optic nerve injury remains a current research hotspot and a difficult point urgently to be solved clinically.

[0005] Currently, the treatment methods for optic nerve injury include conventional neurotrophic factors and hormone drug treatment, as well as emerging stem cell therapy and nerve electrostimulation, etc. On the one hand, the traditional treatment effect is limited, and on the other hand, emerging technologies such as stem cell or gene therapy cannot guarantee in terms of cost, safety, and effectiveness. Therefore, developing drug targets for protecting visual function damage and promoting the regeneration and repair of optic nerve injury is a current research hotspot and a difficult point urgently to be solved clinically in this field. Summary of the Invention:

[0006] The purpose of the present invention is to provide the application of prostaglandin D2 in the preparation of drugs for treating optic nerve diseases.

[0007] The present invention is achieved through the following technical solutions:

[0008] The application of prostaglandin D2 in the preparation of drugs for treating optic nerve diseases, wherein the optic nerve disease is optic nerve injury caused by traumatic optic neuropathy.

[0009] The drug further contains one or more pharmaceutically acceptable carriers or excipients, and is made into any pharmaceutically acceptable dosage form.

[0010] In particular, it is an injection for intravitreal injection.

[0011] Our experimental study first found that prostaglandin D2 (PGD2) has a protective effect on the survival and axonal regeneration of retinal ganglion cells (RGCs), and has important application prospects in the treatment of optic nerve injury caused by traumatic optic neuropathy. Prostaglandin D2 (PGD2), as the most abundant prostaglandin in the mammalian central nervous system, its expression level will be significantly down-regulated with the prolongation of traumatic injury time. Animal experiments have proved that intravitreal injection of PGD2 after optic nerve injury can significantly improve the survival of retinal ganglion cells (RGCs) caused by axonal injury, significantly promote the conduction of cholera toxin B subunit (CTB) to the optic nerve axon, stimulate the regeneration and repair of optic nerve axons, effectively reduce the death of optic nerve ganglion cells caused by trauma, protect neurons, relieve the degeneration of optic nerve ganglion cell axons and promote their signal conduction, thereby effectively improving the optic nerve injury caused by trauma. These results suggest that PGD2 caused by optic nerve injury can effectively alleviate the pathological processes related to optic nerve injury caused by trauma, protect the survival of optic nerve ganglion cells and promote the regeneration and repair after optic nerve injury. It shows its role in repairing optic nerve injury, so it can be used to prepare drugs for treating optic nerve injury caused by traumatic optic neuropathy, that is, intravitreal injection of PGD2 can significantly improve the survival of optic nerve ganglion cells and visual signal conduction, and then relieve the further development of optic neuropathy. And prostaglandin PGD2 is a bioactive molecule, widely distributed in the central nervous system, and its safety is controllable.

[0012] The beneficial effects of the present invention are as follows: Through animal experiments, the present invention first found the application of prostaglandin D2 in the preparation of drugs for treating traumatic optic neuropathy. Intravitreal injection of prostaglandin D2 (PGD2) can significantly improve the survival of optic nerve ganglion cells and the regeneration and repair of optic nerve axons, and is safe and reliable. Description of the drawings:

[0013] Figure 1 It is a schematic diagram of PGD2 promoting the survival of retinal ganglion cells by intravitreal injection;

[0014] Figure 2 It is a diagram of PGD2 promoting the regeneration of optic nerve axons by intravitreal injection. Detailed implementation manners:

[0015] The following is a further description of the present invention rather than a limitation thereof.

[0016] Example 1:

[0017] The prostaglandin D2 (PGD2, Sigma-Aldrich, catalog number P5172) used is a synthetic biopharmaceutical. After being dissolved in PBS, it is prepared into a concentration of 1 mg / ml and aliquoted, and stored at -20°C for short-term storage and at -80°C in an ultra-low temperature refrigerator for long-term storage. In the present invention, PGD2 was injected on the 2nd day after injury. The injection method was intravitreal injection, and a microsyringe was used for precise injection. The injection volume for each mouse's single eye was 1 μl; the contralateral eye was injected with the same volume of PBS in the same manner as a control. On the 12th day after injury, cholera toxin B subunit (CTB) was injected into both eyes through the vitreous cavity. On the 14th day after injury, the retina and optic nerve were separated to evaluate the survival of retinal ganglion cells and the level of optic nerve axon regeneration after injury. Among them, the whole retina was subjected to immunohistofluorescence staining: the survival level of retinal ganglion cells was labeled with RBPMS. After retinal spreading, 4-12 fields of view were randomly selected for photographing, and the number of retinal ganglion cells in a single field of view was statistically analyzed by Image J. As Figure 1 shown, PGD2 injection can significantly promote the survival level of retinal ganglion cells after injury. The level of optic nerve axon regeneration can be reflected according to the CTB conduction level through whole mount preparation of the optic nerve. As Figure 2 shown, after intravitreal injection, CTB is absorbed by retinal ganglion cells and transmitted through axons. PGD2 injection can significantly increase the number of optic nerve axons at the same injury distance, that is, promote the ability of optic nerve axon regeneration.

Claims

1. The use of prostaglandin D2 in the preparation of a drug for treating optic neuropathy, characterized in that: The optic neuropathy is optic nerve damage caused by traumatic optic neuropathy.

2. The use according to claim 1, characterized in that: The drug also contains one or more pharmaceutically acceptable carriers or excipients to prepare any pharmaceutically acceptable dosage form.

3. The use according to claim 2, characterized in that: The dosage form is injection.

4. The use according to claim 3, characterized in that: Injection into the vitreous cavity.

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