环状RNA DDX17调控周细胞功能参与糖尿病性视网膜微血管病变的作用机制研究

糖尿病视网膜病变（DR）是重要的致盲性眼病。视网膜周细胞丢失是DR微血管早期重要病理改变，继而启动视网膜血管内皮细胞增殖和病理性新生血管形成，但确切作用机制尚不清楚。环状RNA（circRNAs）是一类重要的基因元件，参与调控众多生理和病理过程。大量研究证据表明circRNAs参与DR微血管病变的发生发展过程。本课题前期实验发现，circDDX17在DR视网膜组织和周细胞中表达增加。本课题拟构建DR小鼠动物模型和高糖损伤周细胞模型，分析circDDX17在DR中的表达规律；体内、外实验干预circDDX17表达，明确circDDX17对周细胞功能和DR微血管病变的影响；基于生物信息和分子生物学技术，阐明circDDX17通过调控周细胞功能参与DR微血管病变的分子机制；临床DR患者组织液中验证circDDX17表达及对原代周细胞功能影响。本课题研究有望为防治DR提供新的理论依据和治疗靶点。

Diabetic retinopathy (DR) is an important leading cause of blindness. Vascular pericyte degeneration is the predominant clinical manifestation of DR, leading to the dysfunction of endothelial and pathological neovascular formation, yet the mechanism governing pericyte degeneration is poorly understood. Circular RNAs are a novel type of endogenous non-coding RNAs, which involved in many physiological and pathological processes. Large studies report that circRNAs mediate the development of DR microvascular dysfunction. Here, we found that circDDX17 was upregulated in pericytes and DR mouse retinas. We aim to use STZ induced DR mouse in vivo and high glucose stimulated pericytes in vitro to investigate the expression of circDDX17; Intervening the expression of circDDX17 to clarify the impact on pericyte and microvascular degeneration of DR; Using bioinformatics and molecular biology technology to clarify the mechanism of circDDX17 on pericyte degeneration and DR microvascular dysfunction. The expression of circDDX17 in DR patients’ retinas and those effects on primary retinal vascular pericyes. In conclusion, our study is expected to provide a new therapeutic target for the prevention and treatment of DR.