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Application of PDL1 antibody in retinal nerve injury and neurodegenerative eye disease

A retina and antibody technology, applied in the direction of antibodies, sensory diseases, cardiovascular system diseases, etc., can solve problems such as endangering visual function and lack of treatment methods, and achieve the effect of improving phagocytosis, protecting visual function, and improving thinning

Pending Publication Date: 2022-08-09
ZHONGSHAN OPHTHALMIC CENT SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Such diseases seriously endanger human visual function and have become increasingly prominent major refractory blinding eye diseases, including dry age-related macular degeneration (AMD), retinitis pigmentosa (RP) and Stargardt disease, etc., and there is still no effective clinical treatment treatment method
At present, there is no report on the application of anti-PDL1 antibody to regulate the phagocytosis of retinal microglia and treat retinal nerve damage and neurodegenerative eye diseases

Method used

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  • Application of PDL1 antibody in retinal nerve injury and neurodegenerative eye disease
  • Application of PDL1 antibody in retinal nerve injury and neurodegenerative eye disease
  • Application of PDL1 antibody in retinal nerve injury and neurodegenerative eye disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1 Construction of disease model

[0036]Retinal nerve damage and neurodegenerative eye diseases, including dry age-related macular degeneration (AMD), retinitis pigmentosa (RP) and Stargardt disease, are a large class of retinal photoreceptor cell damage, degeneration and apoptosis as pathological features. There is currently no effective treatment for the disease. Retinal nerve damage and neurodegenerative eye disease are a complex process with various pathogenic factors. At present, there is no animal model that can fully simulate the real situation of human diseases, and there is no unified animal model. The retinal photoreceptor cells are damaged in mice. Models are broadly divided into two categories: inducible and genotype.

[0037] In order to fully illustrate the related therapeutic effects of anti-PDL1 antibody on retinal nerve damage and neurodegenerative eye diseases, this example includes chemical (MNU)-induced retinal nerve damage, light-induced re...

Embodiment 2

[0054] Example 2 H&E staining of paraffin sections to observe retinal structural changes

[0055] (1) On the sampling day of the chemical-induced retinal nerve injury mouse model in Example 1, the mice were sacrificed, the eyeballs were removed, and placed in FAS mixed fixative for 24 hours;

[0056] (2) Dehydration in gradient ethanol for 12 hours, followed by soaking in xylene for 2 hours, and soaking in paraffin at 65°C for 3-4 hours for permeabilization and wax soaking;

[0057] (3) The tissue is packaged by the automatic embedding machine, and the 3-4 μm section obtained by the microtome is attached to the slide;

[0058] (4) H&E staining: dewaxing with xylene, washed with 100%, 95%, and 75% gradient alcohol until hydration; immersed in hematoxylin for 10-15 minutes for staining, washed with running water; differentiation and blue return: 1% hydrochloric acid alcohol Differentiate for 1-2 seconds, blue with saturated ammonia water for several seconds, rinse with running ...

Embodiment 3

[0060] Example 3 In vivo measurement of retinal thickness by optical coherence tomography

[0061] (1) On the day when the mouse model of light-induced retinal nerve injury was established in Example 1, the retinas of the mice in the above groups were scanned with an optical coherence tomography scanner (Heidelberg, Germany). The mice to be examined were anesthetized by intraperitoneal injection of 0.5% sodium pentobarbital (0.1mL / 10g);

[0062] (2) Dilate the pupils of mice with compound tropicamide eye drops, and pay attention to dripping water to keep the cornea moist, adjust the body position of the mice, fully expose the fundus, and scan the optic disc in two ways: radial and rectangular;

[0063] (3) The Heidelberg EyE Explorer License Manager 3.0.1 software was used to measure and analyze the results. In three-dimensional imaging, the average thickness of the retina in a circular area with a radius of 1.5 mm from the optic disc was measured.

[0064] Test results such ...

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Abstract

The present invention relates to the use of anti-PDL1 antibodies for the treatment of retinal nerve injury and neurodegenerative eye disease. According to the invention, three mice with retinal nerve injury and neurodegenerative eye disease are constructed, and are subjected to ERG, OCT and Hamp; proved by intravitreal injection of the anti-PDL1 antibody, the retinal nerve cell injury of a diseased mouse can be remarkably reduced, the visual function is protected, and the retinal thinning is delayed. In-vivo cell phagocytic experiments prove that the anti-PDL1 antibody can enhance the phagocytic function of retina microglia cells, promote phagocytic apoptotic neurons of the retina microglia cells, reduce retinal inflammation and promote recovery of visual functions. The invention provides experimental basis and theoretical basis for the anti-PDL1 antibody to treat the retinal nerve injury and the neurodegenerative eye disease, and the anti-PDL1 antibody has a clear conversion application prospect in the preparation of a medicinal preparation for treating the retinal nerve injury and the neurodegenerative eye disease.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, in particular to the application of anti-PDL1 antibodies in the preparation of medicines for treating retinal nerve damage and neurodegenerative eye diseases. Background technique [0002] Retinal nerve damage and neurodegenerative eye diseases are a large class of diseases characterized by damage, degeneration and apoptosis of retinal photoreceptor cells. These diseases seriously endanger human visual function and have become increasingly prominent major refractory blindness-causing diseases, including dry age-related macular degeneration (AMD), retinitis pigmentosa (RP) and Stargardt disease. treatment method. Microglia are the safety guards of the retina, monitoring and maintaining the immune homeostasis of the retina. When photoreceptor cell damage or apoptosis is found, damage-related pattern molecules rapidly activate microglia, which deform and phagocytose these damage-related cells. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K47/02A61P9/10A61P27/02
CPCA61K39/3955A61K47/02A61P27/02A61P9/10
Inventor 柳夏林何嫦刘妍倪弼砚周恬杨紫琪
Owner ZHONGSHAN OPHTHALMIC CENT SUN YAT SEN UNIV
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