CCR3在年龄相关性黄斑变性发病的分子机理研究

老年黄斑变性（AMD）脉络膜新生血管（CNV）形成是老年人视力丧失的主要病因。研究显示CCR3在CNV中特异性表达，小鼠激光诱导CNV中VEGF受体和CCR3可能通过Notch信号通路进行调节，但具体机制不清楚。我们前期研究显示RPE光损伤后VEGF及受体、CCR3及配体存在相似变化，提示慢性光损伤中CCR3及配体与VEGF受体有关联，可能存在某种调节通路。我们推测RPE细胞中CCR3配体和VEGF受体通过Dll4-Notch信号通路进行调节，是自然状态下CNV发生的分子机制。本课题拟采用光损伤RPE细胞及基因敲除Ccl-2-/-和CCR3-/-小鼠作为模型，运用细胞培养、RT-PCR、ELISA、western-blot和si-RNA等技术，研究光损伤和CNV发生过程中Dll4-Notch信号通路及各因子的变化。此研究将有助于揭示CCR3 和VEGF受体在AMD的CNV发生的分子机理。

Age-related macular degeneration ( AMD ) and choroidal neovascularization ( CNV ) formation is the main cause of vision loss in old people. Recent studies show that CCR3 expressed in CNV. Laser induced CNV mouse model showed VEGF receptor and CCR3 may regulated by Notch signal pathway, however the specific mechanism is not clear. Our previous studies showed CCR3 ligands and VEGF receptor had similar changes in RPE cells after photic injury, which suggested CCR3 ligand and VEGF receptor are associated in chronic light damage, and maybe they have the same regulatory pathway. We hypothesized that in CCR3 ligand and VEGF receptor regulated by Dll4-Notch signal pathway in RPE cells, and it is the molecular pathogenesis of CNV in natural condition. In this study, we use the light damaged RPE cells and Ccl-2 - / - and CCR3 - / - mice models, observe the changes of Dll4-Notch signal pathway and the various factors in pathogenesis of CNV. We will use cell culture, RT-PCR, ELISA, Western-blot and si-RNA technology. This study will be helpful to reveal the role of CCR3 and VEGF receptors in the molecular mechanism of CNV.