Application of selective autophagy activator QX77 in preparation of medicine for intervening or treating diabetic retinopathy

A diabetic retinal, selective technology for drug combinations, metabolic diseases, sensory diseases, etc.

Active Publication Date: 2022-04-29
TONGJI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, since the current treatment methods are mostly aimed at the late stage of the disease, and all have certain side effects and prognostic risks, research on the molecular mechanism and treatment methods for the early stage of the disease is imminent

Method used

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  • Application of selective autophagy activator QX77 in preparation of medicine for intervening or treating diabetic retinopathy
  • Application of selective autophagy activator QX77 in preparation of medicine for intervening or treating diabetic retinopathy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1: Diabetic Rat Model Construction and Vitreous Drug Injection

[0029] 1.1 Rat preparation: 4 W SD rats with a weight of about 140 g were purchased from Slack Company and kept in the SPF room of Tongji University Animal Center. Rats were randomly divided into three groups, normal control group (NC), diabetic group (DM), diabetic retinal injection group (DM+QX77).

[0030] 1.2 Modeling by intraperitoneal injection: the rats were starved for 24 hours before the experiment. A single intraperitoneal injection of STZ (60 mg / kg body weight) was used to induce diabetes, and the normal control group was intraperitoneally injected with an equal volume of citric acid solution; 24 hours later, blood was taken from the tail to measure blood sugar, and rats with a blood sugar value higher than 250 mg / dL were used for the test. For intravitreal injection, rats below 250 mg / dL will be excluded.

[0031] 1.3 Intravitreal injection: Rats were anesthetized by intraperitoneal i...

Embodiment 2

[0032] Embodiment 2: SD rat electroretinogram ERG detects physiological function

[0033] 1.1 Instruments: APS Automatic Visual Electrophysiology Tester (APS-2000) was purchased from Chongqing Kanghua Technology Co., Ltd.

[0034] 1.2 Preparation of the rats: the day before the visual electrophysiological function test, the SD rats were transferred to a dark room for dark adaptation. On the day of the experiment, rats were anesthetized by intraperitoneal injection of 2% sodium pentobarbital (1mL / 500g body weight), 1× Sumianxin (0.1ml / 200g) for muscle relaxation, and then a drop of 0.5% tropicamide was given to dilate the pupils ( Wuxi Shanhe Group, Jiangsu, China), a drop of 0.4% oxybucaine hydrochloride topical anesthesia (Eisai Co Ltd, Tokyo, Japan), and a little conductive paste was applied to each eye. Insert the electrodes: connect the ground wire to the tail of the rat, connect the negative electrode between the ears of the rat, and connect the positive electrode to the...

Embodiment 3

[0037] Example 3: Preparation of retinal frozen sections

[0038] 1.1 Eyeball preparation: Eyeball samples were collected from SD rats treated with drugs at different time points. After the SD rats were killed by dislocation, the eyeballs were carefully removed, and the optic nerve was preserved;

[0039] 1.2 Fix: place in 4% paraformaldehyde to fix overnight;

[0040] 1.3 Dissection: dissect the eyeball along the upper edge of the corneoscleral limbus under a dissecting microscope, carefully remove the cornea, iris and lens to form a complete optic cup, and pay attention to gentle operation to prevent retinal detachment;

[0041] 1.4 Dehydration: overnight dehydration with 30% sucrose;

[0042] 1.5 Embedding: embed with tissue embedding solution OCT at 4°C and equilibrate overnight;

[0043] 1.6 Quick freezing with liquid nitrogen: Quickly freeze the eyeballs with liquid nitrogen, and make the eyeballs as vertically centered as possible before freezing. Store frozen sample...

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PUM

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Abstract

The invention provides application of a selective autophagy activator QX77 in preparation of a medicine for intervening or treating diabetic retinopathy. The research finds that the content of a glial cell maturation factor GMFB in a DR early vitreous body is greatly increased, and the glial cell maturation factor GMFB is used as a cell factor to influence a CMA autophagy pathway of a retina, so that the lesion process of DR is accelerated. Through screening, it is found that the selective autophagy activator QX77 can activate a CMA autophagy pathway in the retina, reduce apoptosis of optic nerve cells and protect normal physiological functions of the retina, so that the morbidity process of diabetic retinopathy is delayed. Meanwhile, the QX77 can delay or treat DR in the early morbidity stage as a small molecule medicine, and is convenient to operate and easy to prepare and obtain.

Description

technical field [0001] The invention relates to the technical field of diabetic retinopathy treatment, in particular to the application of selective autophagy activator QX77 in the preparation of drugs for intervening or treating diabetic retinopathy. Background technique [0002] Diabetic retinopathy (DR) is a specific microvascular complication of diabetes. It is chronic, progressive, and potentially harmful to vision. It is the leading cause of blindness in the working population and the elderly. There are more than 93 million DR patients worldwide, of which 17 million suffer from proliferative DR (proliferative DR, PDR), and 28 million suffer from vision-threatening DR (vision threatening DR, VTDR). According to the severity of the lesion and the formation of new blood vessels, DR can be divided into NPDR and PDR. The main fundus manifestations of NPDR are retinal microvascular tumors, punctate and patchy retinal hemorrhages, capillary occlusion, and retinal edema, amon...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/538A61P27/02A61P9/10A61P3/10
CPCA61K31/538A61K9/0019A61K9/0048A61P27/02A61P9/10A61P3/10Y02A50/30
Inventor 吕立夏徐国彤刘彩莹王娟张介平高芙蓉金彩霞田海滨徐晶莹欧庆健陈浩
Owner TONGJI UNIV
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