视网膜退行性疾病是以进行性感光细胞和视网膜色素上皮细胞（RPE）凋亡为特征的致盲性眼病，线粒体损伤引起的RPE细胞功能障碍是此类疾病的始动因素，通过自噬选择性清除损伤线粒体可维持RPE细胞稳态。研究表明PINK／Parkin信号通路是调控线粒体自噬的关键信号通路，Clec16a是该通路重要调控因子。因此本课题拟以RPE细胞内的PINK／Parkin信号通路为靶点，以RCS大鼠模型以及氧化应激细胞模型为研究对象，通过基因转染体内外干预Clec16a的表达，应用荧光标记、分子生物学、线粒体功能检测、线粒体动力学相关蛋白检测、电生理检测等手段，阐明Clec16a调控RPE细胞PINK／Parkin通路的关键分子过程，分析PINK／Parkin通路调控RPE细胞线粒体自噬的具体机制，探讨线粒体自噬干预对于RPE细胞凋亡的保护作用，从而为视网膜退行性疾病发病机制研究以及治疗手段的探索提供重要理论依据

Many ocular fundus disease such as age-related macular degeneration(AMD) and retinitis pigmentosa(RP) are retinal degeneration diseases, which may lead to visual loss and be difficult to treat. The retinal pigment epithelial(RPE) cells dysfunction caused by mitochondrial damage is the important reason for this kind of diseaseds. Mitophagy is a process referred to mitochondria degeneration in time via selective autophagy. Many study have shown that abnormal activation of PINK／Parkin singnaling pathway can control the mitophagy. Clec16a is an important inhibitor of PINK／Parkin pathway. Overexpression of Clec16a prevent the abnormal the activation of the PINK／Parkin pathway and further provide the mitophagy. In this project, we will target at the Clec16a in RPE to investigate the effect of Clec16a on the regulation of PINK／Parkin pathway activation, promotion mitophagy and inhibition of RPE cell apoptosis by using RCS rats as animal model(in vivo) and H2O2-induced cell model(in vitro). Our in vivo and in vitro results will provide the first insight into the mechanism by which Clec16a mediated PINK／Parkin pathway to promote mitophagy and inhibit RPE apoptosis. Therefore, our study will evaluate if Clec16a represents a novel therapeutic target to control retinal degeneration disease, which has a profound theoretical and clinical significance.