EPO对糖尿病性视网膜前膜形成与发展的作用及机理研究

项目名称： EPO对糖尿病性视网膜前膜形成与发展的作用及机理研究

项目编号： No.81200693

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 胡六梅

作者单位： 同济大学

项目金额： 23万元

中文摘要： 糖尿病性视网膜病变（DR）是导致眼盲的重要疾病，抑制糖尿病性视网膜前纤维血管膜（dERM）形成与发展是挽救PDR患者视功能的关键。但目前干预治疗的药物研究较少，主要是作用机制尚未完全明确。我们发现促红细胞生成素（EPO）负反馈调节VEGF，还通过Müer细胞下调视网膜中IL-1β和TNF-α的表达，而且能减轻糖尿病视网膜胶质化反应。由此推测EPO可能主要通过调节Müer细胞中细胞因子表达，细胞骨架及细胞生物学行为改变等在dERM形成与发展中发挥作用。本项目建立模拟dERM的细胞模型，用免疫荧光、GST pull down、细胞划痕实验等方法研究EPO如何影响与dERM细胞共培养的Müer细胞中促纤维细胞因子的表达与释放，基质金属蛋白酶与其组织抑制剂的表达比例，细胞骨架及细胞生物学行为改变，从而明确EPO在dERM形成与发展中的作用及机理，为治疗DR提供依据和指导。

中文关键词： 促红细胞生成素；Müer细胞；糖尿病性视网膜病变；糖尿病性视网膜前膜；纤维化

英文摘要： Diabetic retinopathy (DR) is one of the major diseases leading to blindness, and inhibiting formation and development of diabetic fibrovascular epiretinal membrane (dERM) is the key to save visual function for PDR patients. However, less studies exist about drugs for therapy of dERM, especially its underline mechanism is not completely understood. We found that erythropoietin (EPO) negatively regulated VEGF, and down-regulated expressions of IL-1β and TNF-α by Müer cells in diabetic retina, furthermore EPO could reduce Müer cell gliosis in diabetic retina. It is speculated that EPO may play a role in dERM formation and development mainly by suppressing pro-angiogenic factor, regulating cytoskeletal and cell biological behavior in Müer cells. The project establishes a novel co-culture model for dERM, and employs immunofluorescence, GST pull down, and cell scratch assays to study how EPO affects expression and release of pro-fibrous cytokines, the ratio of matrix metalloproteinases and their tissue inhibitors, and cytoskeleton and cell biological behavior changes in Müer cells. The obtaining data derived from the dERM model will result in explaining the role of EPO via Müer cells in the dERM formation and development, and indicating targets for the treatment of PDR.

英文关键词： Erythropoietin；Müer cells；Diabetic retinopathy；Diabetic epiretinal membrane；fibrosis