小胶质细胞失稳态在光损伤视网膜变性中作用研究

项目名称： 小胶质细胞失稳态在光损伤视网膜变性中作用研究

项目编号： No.30872825

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 徐格致

作者单位： 复旦大学

项目金额： 34万元

中文摘要： 视网膜变性疾病的分子病理机制及治疗仍是目前研究的难点。近年来小胶质细胞的作用受到重视。光感受器损伤后激活小胶质细胞，导致进一步神经元损伤已得到证实。但光感受器损伤和小胶质细胞激活之间的分子对话机制仍不清楚，阻止该过程成为从同一途径延缓视网膜变性发展的关键。研究提示趋化因子Fractalkine 可能是二者功能对话的重要介质。本研究拟采用光损伤视网膜模型、体外光感受器和小胶质细胞共培养模式，研究Fractalkine 及受体CX3CR1 信号在光感受器损伤后的时空变化，着力于分析该信号的变化规律及与视网膜小胶质细胞激活、神经元凋亡之间潜在的关系，并深入探讨其调控小胶质细胞激活的细胞内信号途径，阐明神经元损伤和小胶质细胞激活之间的分子机制，为延缓视网膜变性疾病的进展开拓新治疗思路。

中文关键词： 视网膜变性；趋化因子；信号通路；小胶质细胞；光感受器；

英文摘要： Retinal degenerative diseases have been a major focus of current research, with much effort being devoted to understanding the pathological cellular changes and the theropy method. Recent results indicate that photoreceptor damage lead to microglial activation, which would be driven by the further loss of photoreceptors. Although the involvement of microglia is certain, the relationship between photoreceptor damage and microglial activation remains poorly understood. Mounting evidence suggest that the ligand-receptor pair fractalkine/CX3CR1 appear to be an ideal candidate to mediate neural/microglial interaction. In this work, we try to investigate the cross-talk between injured photoreceptors and activated retinal microglia, focusing on the role of fractalkine and its receptor CX3CR1 in light-induced photoreceptor degenerative disease using both in vivo and in vitro models. We will evaluate the spatial and temporal relationship among photoreceptor apoptosis, fractalkine/CX3CR1 impairment, and microglial activation/ migration. Furthermore, we will explore the downstream intracellular signal transduction pathways. The purpose of this study is to find a novel therapeutic target to regulate inflammation and photoreceptor survival in light-induced retinal degeneration.

英文关键词： retinal degeneration;chemokine;signaling pathway;microglia;photoreceptor;