研究发现HIF-1α在视网膜新生血管（RNV）发生中起重要作用，但其调节机制尚不清楚。SENP1是HIF-1α上游的一个重要调控因子。我们预实验发现：低氧诱导SENP1表达增加，促进HIF-1α去SUMO化，调节视网膜血管内皮细胞（RMECs）增殖、迁移和VEGF分泌。故提出假说：SENP1调控HIF-1α去SUMO化修饰及VEGF分泌，影响RNV发生。本课题拟首先在低氧刺激的RMECs细胞模型中研究SENP1对HIF-1α去SUMO化修饰和核转位的影响；接着分析HIF-1α入核对SENP1表达的正反馈促进作用；在此基础上，进一步分析干预SENP1对RMECs增殖、迁移、VEGF分泌、内皮管腔形成等的影响；最后在OIR动物模型中干预SENP1，明确SENP1调控HIF-1α去SUMO化修饰，对RNV发生的影响。研究结果有望为探索低氧诱导RNV的发生机制及其防治靶点提供理论和实践依据。

Retinal neovascularization (RNV) is a major cause of vision loss in patients with ischemia-induced retinopathy. Previous studies show that HIF-1α plays an important role in the processes of RNV, but the underlying mechanism remains uncovered. SENP1 is one of the most important factors in the upstream signals of HIF-1α. The results of our preliminary experiments suggested that: hypoxia induced the expression of SENP1, promoted the deSUMOylation of HIF-1α, and regulated the proliferation, migration and VEGF secretion of retinal vascular endothelial cells (RMECs). Accordingly, we proposed the following hypothesis: SENP1 regulates HIF-1α deSUMOylation and VEGF secretion, affecting the occurrence and development of RNV. In the present study, we are to first investigate the effect of SENP1 on the deSUMOylation and nuclear translocation of HIF-1α in hypoxia-stimulated RMECs. The positive feedback loop between HIF-1α and SENP1 will be analyzed, and the effects of SENP1 on the proliferation, migration, VEGF secretion and the formation of endothelial lumen in RMEC are going to be examined subsequently. Lastly, SENP1 gene will be knocked out in animal models of OIR to determine the effect of SENP1 on the deSUMOylation of HIF-1α. This study may lead to more in-depth understanding of the mechanism of RNV and provide new therapeutic target of RNV related retinopathies.