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Application of GMFB (glia maturation factor beta), GMFB disrupter and application of GMFB disrupter

An interfering agent, technology of diabetic retina, applied in the target of therapeutic intervention, GMFB interfering agent and application of GMFB interfering agent, early diagnosis biomarker of diabetic retinopathy, can solve problems such as no reports of GMFB function, To achieve the effect of protective vision function

Active Publication Date: 2015-12-16
TONGJI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The currently used cytokines related to the progression of DR include the following four categories: (1), factors that regulate innate immunity: IL-1b, IL-10; (2) factors that regulate the activation, proliferation and differentiation of lymphocytes: IL-6 and IL -12; (3) Factors related to the activation of macrophages: TNFa and TGFb (4) chemokines, such as MCP-1, SDF-1, etc., and there is no report on the role of GMFB in DR

Method used

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  • Application of GMFB (glia maturation factor beta), GMFB disrupter and application of GMFB disrupter
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  • Application of GMFB (glia maturation factor beta), GMFB disrupter and application of GMFB disrupter

Examples

Experimental program
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Effect test

Embodiment 1

[0034] Expression of GMFB in different nuclear layers of diabetic retina

[0035] 1. Preparation of diabetic rats: male SD rats weighing 160-180 g were used, and the rats were starved for 24 hours before the experiment. A single intraperitoneal injection of STZ (60mg / kg body weight) to induce DM, and the same volume of citric acid solution was injected intraperitoneally in the normal control group; 24 hours later, blood was taken from the tail to measure blood glucose, and rats with blood glucose values ​​lower than 250mg / dL were given supplementary injections STZ. Blood sugar was measured for 3 consecutive days. Rats with blood glucose exceeding 250 mg / dL for 3 consecutive days were determined as DM rats (rats with blood glucose lower than 250 mg / dL would be excluded). Although the DM rats were prepared, when the eye changes were checked, at least two weeks later, the neural retina, RPE, vascular endothelial cells, BRB, ERG and other changes could be detected to support ret...

Embodiment 2

[0057] Changes of GMFB concentration in the vitreous of STZ-induced TIDM rats with the course of DR

[0058] Adopt STZ to prepare type I diabetes model, the method is the same as in Example 1, collect the vitreous body of diabetic rats at different time points, collect 6-8 rats at each time point, collect respectively, transfer the supernatant after 1000g is centrifuged at 4 degrees for 20 minutes Standby, carry out ELISA detection, and participate in the results figure 2 , figure 2 Among them, Cont is normal control, PI is after postinjection injection, DM is diabetes mellitus, by figure 2 It can be seen that on the first day of elevated blood sugar, GMFB was found to increase significantly, then decreased slightly, and remained at a high level, and gradually decreased from the fourth week, and dropped to a level similar to that of the normal control in the eighth week of the onset of DM . The elisa kit of the GMFB of rats was purchased from Elabscience (article number ...

Embodiment 3

[0076] Interfering with GMFB improves visual function in DR rats

[0077] 1. Prepare the type I diabetes rat model, the method is the same as that in Example 1.

[0078]On the day of onset of STZ-TIDM rats (referring to the first day after the blood glucose concentration of the rats exceeded 250mg / dL for 3 consecutive days), AAV2 / 8-shGMFB3ul was injected into the subretinal cavity, and GFAP immunofluorescence was detected 4 weeks after the injection, indicating that the glue Qualification is suppressed. The effect of AAV2 / 8-shGMFB interference on the visual function of STZ-induced DR is shown in Figure 3.

[0079] See results Figure 3a , Interference with GMFB in the retina of DR rats decreased the expression of glial fibrillary acidic protein (GFAP). 4',6-diamidino-2-phenylindole (DAPI) is a fat-soluble fluorescent dye that stains the nucleus; Zsgreen is a green label, RPE is the retinal pigment epithelium, and ONL is the outer nuclear layer , INL is the inner core layer...

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Abstract

The invention relates to application of GMFB (glia maturation factor beta) as a biomarker for early diagnosis of diabetic retinopathy and for diabetes progression, application of GMFB as a therapeutic target of diabetic retinopathy, a GMFB disrupter and application of the GMFB disrupter. Compared with the prior art, the invention proves that the GMFB content in vitreous body is significantly improved in early period of diabetes in rats of STZ-induced I type diabetes (TIDM). The invention is the first to prove that GMFB content gradually drops with the development of DR (diabetic retinopathy), therefore the GMFB is applicable to dynamic detection of DR progress; the invention is the first to prove that by interfering GMFB expression in rats of DR, visual function can be protected; and the invention is the first to prove that GMFB mediates retinopathy mechanism, including causing decrease of glutamine synthetase of Muller cell, death of ganglion cells and inducing autophagy of photoreceptor cells.

Description

technical field [0001] The present invention relates to the use of the cytokine GMFB, in particular to the application of GMFB as a biomarker for early diagnosis of diabetic retinopathy and as a target for therapeutic intervention, a GMFB interfering agent and an application of the GMFB interfering agent. Background technique [0002] With the rapid development of my country's economy and the acceleration of the aging process, the prevalence of diabetes (diabetes milletus, DM) is showing a rapid upward trend, becoming another important chronic disease that seriously endangers people's health after cardiovascular and cerebrovascular diseases and tumors. infectious disease. The World Health Organization predicts that in 2025, the number of diabetic patients in China will reach 300 million. Diabetic Retinopathy (DR), referred to as Diabetic Retinopathy, is the most common complication of diabetes. 1 / 3 of DM patients develop DR, and 1 / 10 suffer from fatal vision-threatening diab...

Claims

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Application Information

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IPC IPC(8): C12Q1/68G01N33/573A61K48/00A61P9/10A61P3/10
CPCA61K48/00C12Q1/68C12Q1/6851G01N33/573C12Q2531/113C12Q2561/113C12Q2563/107
Inventor 徐国彤吕立夏
Owner TONGJI UNIV
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