地图样萎缩（GA）是导致老年黄斑变性（AMD）患者视力不可逆损伤的重要原因，近期大规模临床试验发现抗VEGF治疗后GA发病率增高，其机制不明。我们前期研究发现RPE细胞的VEGF和整合素升高具有协同作用，推测VEGF抗体可能阻断了病理状态下VEGF对整合素双向信号转导通路的调控，加重RPE细胞变性死亡导致GA发生。本研究将通过体内外研究，首先通过PCR Array和悬浮抗体芯片筛选，明确与VEGF相互作用的关键整合素亚基；应用流式细胞仪、RPE细胞吞噬功能定量研究及透射电镜、免疫电镜等方法，结合OCT、FA活体观察，阐明VEGF及其抗体对整合素及其介导RPE细胞功能与存活的影响；通过生物多肽干扰整合素β亚基功能，寻找VEGF对整合素双向信号转导的调控位点，以揭示抗新生血管治疗后GA发生发展的新机制、获得新的干预位点，为AMD的临床诊治提供新的思路。

Geographic atrophy (GA) is the leading cause of vision loss in age-related macular degeneration (AMD) patients. Recently, large-sample clinical trials have revealed the increased incidence of GA after anti-VEGF therapy, but the mechanisms remain elusive. Our previous study found that the expression of VEGF and integrin both increased in RPE cells during the process of choroidal neovascularization, as it causes the inhibited RPE apoptosis. Therefore, we propose the following hypothesis: The interplay between VEGF and Integrin signal can be suppressed by VEGF antibody, leading to RPE apoptosis. Thus long-term use of VEGF antibody will promote the occurrence of GA. Our study will simulate the RPE "anoikis" status in AMD in vitro and in vivo, multiple treated with VEGF antibody. Firstly, PCR array and protein analysis floating chip will be used to screening and determine the key subunit of integrin. Using flow cytometry, RPE phagocytosis assay, PI stain，transmission electron microscope, and immuno-electron microscope to verify the change of integrin expression/activity, and to investigate related RPE function and cell survival. Secondly, we will use biological peptides to interference integrin beta subunit to reveal the key molecular of interplay action between VEGF and Integrin bi-directional signal transduction. It is very hopefully that this project can reveal a novel pathogenesis of GA after anti-VEGF treatment, and to explore and suggested new intervention targets, and to provide new evidence for the clinical treatment of AMD.