O-糖基化修饰参与糖尿病性视网膜病变神经损伤机制研究

项目名称： O-糖基化修饰参与糖尿病性视网膜病变神经损伤机制研究

项目编号： No.81470638

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘堃

作者单位： 上海交通大学

项目金额： 73万元

中文摘要： 糖尿病性视网膜病变（diabetic retinopathy DR）神经损伤早于微血管病变。早期干预的最佳时机在视网膜神经组织发生损伤前进行。糖代谢紊乱所引起的酶促糖基化改变是早期主要的病理生理改变，是启动下游通路的关键因素。本课题在前期研究糖基转移酶、N-糖基化修饰的基础上，进一步探讨酶促糖基化的重要产物O-糖基化修饰中的O-GlcNAc修饰形式参与DR 视网膜神经损害的相关机制，以此作为研究酶促糖基化修饰与DR相关性的切入点。相关研究尚属空白，希望通过研究： O-GlcNAc修饰与视网膜神经节细胞（RGC）凋亡关系；其诱导RGC凋亡的相关调控机制，了解高糖引起的酶促糖基化改变在DR发病中的重要作用；通过蛋白组学研究翻译后修饰过表达蛋白寻找相关研究靶点，为相关干预机制的采用提供实验室基础。

中文关键词： 糖尿病视网膜病变；神经损伤；糖基化修饰；细胞凋亡

英文摘要： As the prevalence of diabetes has continued to rise, diabetic retinopathy ( DR) has become one of the main blinding disease. The key of DR prevention and control is that for early diagnosis of disease and early intervention treatment. The early pathological changes of DR including retinal capillary anomalies and neural injury, the nerve damage often happen earlier more than the capillary pathological changes. The best time for DR treatment is before the appearance of visual function damage, namely the corresponding intervention should be taken before the damage of retina nerve tissue occurred. This study was to take the enzymatic modification of glycosylated change as the breakthrough point, which caused by the glucose metabolic disorder due to hyperglycemia, discusses the mechanism of neural injury related to O-GlcNAc modification which is one of products of the enzyme glycosylation. To know the function of O-GlcNAc modified in the role of cell apoptosis through the research: 1. O-GlcNAc modified directly influence, 2. O-GlcNAc modified influenced the protein related to cell apoptosis and 3. O-GlcNAc modified influence the protein control the cell apoptosis. Offer the research foundation to the related intervention measure for the treatment of DR.

英文关键词： diabetic retinopathy;neural injury;protein glycosylation modification;apoptosis