抗血管内皮细胞生长因子（VEGF）疗法可阻断新生血管生长，但在治疗眼底新生血管性病变及抗肿瘤的过程中发生了抗血管生成治疗抵抗的现象，已有证据表明抗VEGF抵抗通过胞内信号通路的自我调节完成。α晶体蛋白（CRYAA）分子是重要的分子伴侣蛋白，主要通过激活细胞内自我保护信号转导通路而发挥作用。前一个国自然课题结果显示CRYAA具有重要细胞保护作用，在此基础上研究发现CRYAA具有促视网膜血管增生作用，那么CRYAA调控血管新生形成的机制如何呢？项目拟在前期工作基础上进一步探讨CRYAA在眼内新生血管中的作用机制，以缺氧条件下培养的血管内皮细胞及缺氧诱导基因敲除小鼠视网膜新生血管形成、激光诱导脉络膜新生血管为模型，运用细胞培养、RT-PCR、Western-blot、ELISA及基因转导等技术，在细胞水平与动物水平研究CRYAA对新生血管的影响与分子机制，为临床抗VEGF治疗提供新方法或辅助手段。

Anti-vascular endothelial growth factor (VEGF) therapy can block the growth of neovascularization , but there is resistance in the anti -VEGF treatment and anti-tumor therapy .There is evidence that anti- VEGF resistance is induced by intracellular self-regulation of the intracellular signal transduction pathway . α A -crystallin(CRYAA) is an important molecular chaperone protein .It plays an important role in cell protecting by activating intracellular signal transduction pathways . Our last country natural subjects showed the important cytoprotective role of CRYAA. Based on this, we take in sight the role of CRYAA in retinal neovascularization .Our previous research found out that CRYAA can have pro- angiogenic effect . How dose CRYAA function ,whether independent or on VEGF signal pathway ? What is the exact mechanism like ? This project intends to further explore the functional mechanism of CRYAA in retinal neovascularization.We research on hypoxia cultured vascular endothelial cells and oxygen induced retinal neovascularization model of CRYAA-knockout mice. Cell culture , RT -PCR, Western-blot, ELISA , and gene transfaction techniques are used both in animal and cellular level for the research of CRYAA function on retinal neovascularization . Looking forward to new therapy for anti-VEGF in clinical treatment.