糖尿病视网膜病变与视网膜静脉阻塞是世界范围内诱发成年人视力丧失的两大首要缺血性视网膜病变。申请人前期工作显示VEGF能够诱发视网膜血管表达VEGFR1白细胞瘀滞参与血管闭塞及缺血,但黏附后白细胞参与视网膜血管闭塞的机制尚不十分明确。白细胞源性微粒有促炎促凝等生物活性而备受关注，申请人亦发现其在糖尿病视网膜病变患者玻璃体中表达升高，且抗VEGF应用后明显下降。在此基础上，本课题假设VEGF可激活VEGFR1释放白细胞源性微粒，通过促凝、扩大炎症反应及破坏血管内皮细胞参与视网膜血管闭塞发生。本项目将建立VEGF转基因动物模型并体外刺激外周血白细胞，检测白细胞源性微粒体表达；探究其对组织因子/组织因子抑制因子调节，炎症因子表达及诱发内皮细胞凋亡等，发挥促炎促凝及内皮细胞损伤作用，诱发视网膜血管闭塞；探究VEGF通过启动VEGFR1通路诱发白细胞源性微粒释放机制，为缺血性视网膜病变诊疗提供新思路。

Diabetic retinopathy and retinal vein occlusion are the top two vision-threating eye diseases for adults worldwide without clear mechanism clarified. As what we reported before, VEGF as the predominant factors can induce large amount of leukocyte expressed VEGFR1 recruitment and plugging the retinal vessels, which cause vascular occlusion and ischemia and hypoxia subsequently. However, the mechanism involved was not clear yet. Leukocyte-derived microparticles are hotshot due to their effect of proinflammation and procoagulation . Leukocyte-derived microparticles were increased in vitreous collected from diabetic retinopathy patients, and decreased with anti-VEGF treatment.Accordingly, we hypothesize that VEGF induce the release of microparticles via activation of VEGFR1, which promote coagulation, inflammation and endothelial injury, and then enhance the progression of retinal vascular occlusion. In this project, we would like to set up VEGF overexpressed animal model and peripheral blood leukocytes stimulated with VEGF, and perform flow cytometry to test leukocyte derived microparticles ;we will pursue their effect on the regulation of TF/TFI balance, expression of inflammatory factors and damage of endothelial cells, hitherto, cause retinal vascular occlusion. We will look into the mechanism of VEGF release leukocyte derived microparticles via VEGFR1 pathway. These results will promote better understanding of pathology and treatment of retinal ischemic retinopathy.