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Application of NOX2 specific inhibitor in preparation of retinal degeneration drugs

A retinal degeneration and inhibitor technology, which is applied in drug combinations, pharmaceutical formulations, organic active ingredients, etc., can solve the problems of impractical apocynin retinal degeneration, inaccurate mechanism of action of apocynin, poor NOX2 inhibitory effect, etc., and achieve delayed loss of photoreceptor cells , increased thickness, clear mechanism of action

Active Publication Date: 2022-03-01
BEIJING TONGREN HOSPITAL AFFILIATED TO CAPITAL MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Document "Sorce, S., K.H.Krause, and V.Jaquet.Targeting NOX enzymes in the centralnervous system: therapeutic opportunities. Cell Mol Life Sci.2012; 69(14):2387-407." It is also mentioned that apocynin has The inaccurate mechanism of action, lack of specificity and poor inhibitory effect on NOX2, and the high failure rate of the previous use of antioxidant drugs in the treatment of hereditary retinal degeneration further prove that apocynin is not feasible in the treatment of retinal degeneration

Method used

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  • Application of NOX2 specific inhibitor in preparation of retinal degeneration drugs
  • Application of NOX2 specific inhibitor in preparation of retinal degeneration drugs
  • Application of NOX2 specific inhibitor in preparation of retinal degeneration drugs

Examples

Experimental program
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Effect test

experiment example 1

[0040] Experimental Example 1: Verification of the NOX2 gene as a therapeutic target of drugs for the treatment and / or prevention of hereditary retinal degeneration

[0041] 1. Crossbreeding NOX2 knockout (NOX2KO) mice with rd1 mice to obtain F1 generation mice

[0042] Four male NOX2 gene knockout mice with gp91phox- / Y rd1W / W gp91phox- / Y rd1W / W (that is, B6.129S-Cybb with NOX2 gene knockout on X chromosome tm1Din / J mice (purchased from Jackson Laboratory, JAX code: 002365) were crossed with eight gp91phox+ / +rd1+ / + female rd1 mice (purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd.) to obtain Male hybrid F1 mice with gp91phox+ / Y rd1W / + genotype and female hybrid F1 mice with gp91phox+ / -rd1w+ genotype.

[0043] In order to verify the correctness of the genotype of the F1 generation mice, the primers in Table 1 were used to amplify the genome of the F1 generation mice by PCR, and then the amplified products were analyzed by gel electrophoresis. The a...

experiment example 2

[0088] Experimental Example 2: Verification of NOX2-specific inhibitors as drugs for the treatment and / or prevention of hereditary retinal degeneration

[0089] 1. Experimental method

[0090] 1.1. Retinal tissue slice (VAS2870)

[0091] Inject 0.5 μg of VAS2870 dissolved in 1 μL of 10% (w / v, g / 100mL) DMSO (purchased from Sigma, product number SML2967) into the vitreous cavity of rd1 mice (day-old 9d) with a PI-100 microinjector, The final effective concentration in the vitreous cavity was 50 μg / mL, and the contralateral eye was injected with the same dose of 10% DMSO as the control group. On the 5th day after the injection (the peak of apoptosis), the rd1 mice were anesthetized and killed by overdose of chloral hydrate, and the eyeballs were quickly removed. As for the OCT embedding medium, they were quickly placed in liquid nitrogen and stored in a -80°C refrigerator until later. Use; make 7 μm frozen sections through the optic disc and ora serrata, 12 eyes of 6 mice in ea...

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Abstract

The invention relates to application of a NOX2 specific inhibitor in preparation of retinal degeneration drugs, and belongs to the technical field of biology. The invention provides application of a NOX2 specific inhibitor in preparation of a medicine for treating and / or preventing retinal degeneration. Research finds that compared with a hereditary retinal degeneration animal model rd1 mouse, loss of retinal outer nuclear layer photoreceptor cells of an NOX2 gene defect rd1 mouse model is obviously delayed, activation of microglial cells is obviously inhibited, and expression of NOX2 in the microglial cells is obviously reduced, and compared with the rd1 mouse model, research finds that the loss of the NOX2 gene defect rd1 mouse model is obviously delayed. According to the present invention, the thickness of the retina outer nuclear layer of the rd1 mouse model injected with the NOX2 specific inhibitor in vivo is significantly increased, the microglial cell activation is significantly inhibited, the NOX2 expression in the microglial cells is significantly reduced, and the NOX2 specific inhibitor has characteristics of clearer action mechanism and stronger specificity compared with the apocynin;

Description

technical field [0001] The invention relates to the application of NOX2 specific inhibitors in the preparation of retinal degeneration medicines, and belongs to the field of biotechnology. Background technique [0002] Primary retinitis pigmentosa (RP) is a group of hereditary eye diseases that cause progressive photoreceptor cell apoptosis, with an incidence rate of 1 / 3000-4000, and has led to blindness of more than 1.5 million adults worldwide. Although gene and stem cell therapy have made some progress in the treatment of RP, due to the complexity of the RP phenotype or the potential problems of the technology itself, its widespread clinical application is not yet realistic. The study of the common pathological mechanism is still very important. Even if the cause of the disease (gene mutation) cannot be fundamentally changed, drug treatment targeting the core link of its common pathogenic mechanism can still delay the loss of photoreceptor cells, delay the blinding time ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/437A61K31/519A61K38/17A61P27/02A61P9/10
CPCA61K45/00A61K31/437A61K31/519A61K38/1709A61P27/02A61P9/10
Inventor 曾惠阳刘谦武珅王宁利
Owner BEIJING TONGREN HOSPITAL AFFILIATED TO CAPITAL MEDICAL UNIV
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