糖尿病视网膜病变(Diabetic Retinopathy，DR)是工作年龄人群的第一位致盲性眼病，其发病机制尚未完全阐明。最新研究显示，补体调控在DR的炎症损伤中发挥关键作用。本课题组前期研究发现（1）DR患者血清及玻璃体腔液中补体下游调控因子C5a及VEGF表达增高，且与疾病参数相关；（2）遗传学研究显示C5基因与DR发病风险及临床表型相关；（3）以Müller细胞为研究对象，外源C5a干预可上调炎症因子及TLR-4的表达。由此我们推测：C5a/C5aR可能通过TLR-4信号通路参与DR的炎症损伤。为证明该假说，本项目将在上述发现基础上，以C5a/C5aR为切入点，通过临床对照研究进一步论证其与DR的相关性，构建糖尿病大鼠视网膜损伤模型及Müller细胞高糖模型，结合现代分子生物学的技术手段探索补体C5a/C5aR介导DR炎症损伤的分子机制，为DR的临床治疗提供新思路和新靶点。

Diabetic retinopathy (DR) has become the leading cause of blindness among working-age group, the pathogenesis has not been fully elucidated. Recent studies show that complement regulation plays a key role in the inflammation process of DR. In our previous study, we found that (1) the expression of C5a and VEGF was increased in the serum and vitreous humor of patients with DR, and related to disease parameters; (2) genetic study showed that C5 was related to the risk of DR and its clinical phenotype; (3) taking müller cell as the research object, exogenous C5a intervention could upregulate the expression of inflammatory factors and TLR-4. It is suggested that C5a/C5aR may participate in the inflammatory damage of DR through TLR-4 signaling pathway. In order to prove the hypothesis, based on the above findings, this project will take C5a/C5aR as a key point, further consolidate the correlation between C5a/C5aR and DR through clinical case-control study; by constructing diabetic rat model and müller cell model cultured with high glucose, we will explore the molecular mechanism of DR inflammation mediated by C5a/C5aR in combination with modern molecular biology technology, so as to provide new ideas and targets for the clinical treatment of DR.