糖尿病视网膜病变（DR）是主要致盲性疾病，血视网膜屏障（BRB）损伤导致的血管渗漏是DR的重要病理特征。研究表明长链非编码RNA（lncRNA）在DR病理改变中起到重要调控作用。在前期研究中，我们对II型糖尿病条件下BRB细胞模型进行RNA测序，发现新型的lncRNA APOL1表达上调，蛋白精氨酸甲基化转移酶7（PRMT7）表达下调，且APOL1可在细胞中与PRMT7直接结合。我们遂提出假说，APOL1可经直接结合并竞争性抑制PRMT7而调控II型糖尿病视网膜血管渗漏。为证明此假说，我们拟在II型糖尿病小鼠中研究APOL1对渗漏的作用；在BRB体外模型中，检测APOL1竞争性抑制PRMT7对下游转录相关因子甲基化的影响；探索PRMT7调控的基因网络；检测DR患者玻璃体液中APOL1和PRMT7的改变并分析临床相关性。本课题将阐明APOL1在DR渗漏中的作用及机制，为DR治疗寻找新靶点。

Diabetic retinopathy (DR) is a major blinding disease. The vascular leakage caused by blood-retinal barrier (BRB) breakdown is an important pathological characteristic of DR. Research has shown that long noncoding RNA (lncRNA) plays crucial regulatory roles in pathological changes of DR. In the preliminary studies, we performed a high-throughput RNA sequencing of the BRB cell culture model under Type II diabetic conditions. We found that the expression of APOL1, a novel lncRNA with unknown function, was significantly upregulated; whereas its predicted RNA binding protein, protein arginine methyltransferase 7 (PRMT7) significantly downregulated. Moreover, APOL1 can directly bind to PRMT7 in cells. We, hence, put forward our hypothesis that APOL1 may regulate retinal vascular leakage through direct binding to consequently competitive inhibition on PRMT7. To prove this hypothesis, we plan to study the effects of APOL1 on retinal vascular leakage in a mouse model of Type II diabetes. In the in vitro BRB model, we are going to examine the influence of APOL1’s competitive inhibition on PRMT7 on methylation of downstream factors related to transcription. Then we will attempt to delineate the gene network regulated by PRMT7. Finally, we will measure the expression levels of APOL1 and PRMT7 in vitreous samples of DR patients and analyze the clinical relevance. This project will elucidate the role and mechanism of action of APOL1 in vascular leakage of DR, thereby facilitating the search for new therapeutic targets for DR.