调控SOX9介导的Müller细胞过度活化对大鼠光损伤视网膜变性的保护作用及其机制研究

项目名称： 调控SOX9介导的Müller细胞过度活化对大鼠光损伤视网膜变性的保护作用及其机制研究

项目编号： No.81500723

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 王鑫

作者单位： 复旦大学

项目金额： 18万元

中文摘要： 视网膜变性疾病的病理机制及治疗是目前研究的难点。这些变性疾病的共同病理过程是视网膜重塑，作为视网膜主要的胶质细胞，Müller细胞过度活化及胶质瘢痕的形成是视网膜重塑的关键环节，但其活化的调控机制尚不清楚。中枢神经系统的研究提示SOX9基因在调控胶质细胞过度活化及细胞外基质（ECM）形成中扮演重要角色。SOX9在成体视网膜仅在Müller细胞表达，申请人前期的研究发现SOX9在光损伤诱导的视网膜变性大鼠中表达上调。故推测，SOX9可能是调控Müller细胞过度活化及ECM沉积的关键靶点。本研究拟采用光损伤诱导的视网膜变性大鼠模型，以SOX9与Müller细胞活化的关系为切入点，观察抑制SOX9表达后对大鼠视网膜光损伤的保护作用；对Müller细胞活性及ECM沉积的影响；探求调控SOX9的信号通路，阐明SOX9在视网膜重塑中的作用机制，为视网膜变性疾病的治疗提供新的思路。

中文关键词： 视网膜变性；；Müller细胞；；SOX9

英文摘要： Currently, the mechanisms and treatment of retinal degenerative diseases are still major research concerns. The common pathological process of these diseases is retinal remodeling. As the principal glial cell, reactivation of Müller cells and glial scars formation play a critical role in the process of retinal remodeling. However, it’s still unknown how this process happens. The studies in central nervous system have indicated that SOX9-upreglutation contributed a lot to reactivation Müller cells and extracellular matrix deposition (ECM). SOX9 is only expressed in Müller cells in mature retina. Our research has shown that SOX9 is upregulated in retinal light damage of rats. And hence, we infer that SOX9 could play an important role in reactivation of Müller cells and ECM deposition. In this study, to explore the role for SOX9 in retinal remodeling, we focus on the relationship between SOX9 and reactivity of Müller cells. We evaluated the neuroprotective effect of reactive depression of Müller cell via down-regulating SOX9 in retinal light damage of rats and investigate the upstream and downstream molecules of SOX9. The results can provide a new clue to retinal degenerative diseases treatment.

英文关键词： retinal degeneration;Müller cell ;SOX9