Abstract：
Diabetic retinopathy (DR) is a blinding disease caused by diabetes, characterized by neovascularization of the retina. The aim of this study was to investigate the roles of epidermal growth factor-like structural domain 7 (EGFL7) on human retinal vascular endothelial cells (HRECS) and retinas from rats with DR. An in vitro model of DR was established through culturing HRECS in high glucose. The in vivo model of DR was established by injecting SD rats with streptozotocin (STZ) to induce diabetes. The differences in the expressed levels of EGFL7, PI3K, AKT, P-AKT and VEGFA in high-glucose cultured cells and retinal tissues of diabetic rats were detected in compared to those in the control group. Stable EGFL7 knockdown cell lines were generated by transfecting HRECS with lentiviral vectors and the effects of EGFL7 knockdown on angiogenesis, cell migration and proliferation were investigated. The results showed that EGFL7, PI3K, P-AKT and VEGFA was increased in cells and tissues under high glucose conditions. Knockdown of EGFL7 downregulated the proliferation, migration and angiogenesis capacity of HRECS, and blocked the PI3K/AKT/VEGFA signaling pathway. Furthermore, overexpression of PI3K reversed the effects of EGFL7 inhibition. These findings provide new ideas for the treatment of neovascularisation in DR.
摘要：
糖尿病视网膜病变(DR)是由糖尿病引起的致盲疾病,以视网膜新生血管形成为特征。这项研究的目的是研究表皮生长因子样结构域7（EGFL7）在人视网膜血管内皮细胞（HRCS）和DR大鼠视网膜中的作用。通过在高糖条件下培养HRCS，建立了DR的体外模型。通过给SD大鼠注射链脲佐菌素（STZ）诱导糖尿病，建立DR的体内模型。EGFL7、PI3K、AKT,与对照组相比，检测高糖培养细胞和糖尿病大鼠视网膜组织中的P-AKT和VEGFA。通过用慢病毒载体转染HRCS产生稳定的EGFL7敲低细胞系，并研究EGFL7敲低对血管生成的影响，研究了细胞迁移和增殖。结果表明,EGFL7、PI3K、在高葡萄糖条件下,细胞和组织中的P-AKT和VEGFA增加。EGFL7的敲除下调了增殖，HRCS的迁移和血管生成能力，并阻断PI3K/AKT/VEGFA信号通路。此外，PI3K的过表达逆转了EGFL7的抑制作用。这些发现为DR中新生血管的治疗提供了新思路。
