外泌体源lncRNA AL591030.1靶向miR-130a促糖尿病视网膜病变发病的机制研究

糖尿病视网膜病变（DR）是一类高致盲性眼病。人视网膜色素上皮（RPE）细胞焦亡促DR发病，而外泌体与细胞焦亡密切相关，但其调控机制很多未知。我们前期使用高糖诱导RPE细胞构建了DR细胞模型，发现miR-130a介导的信号通路能够抑制RPE细胞焦亡；其外泌体中高表达的lncRNA AL591030.1与miR-130a互作，过表达lncRNA AL591030.1时，miR-130a表达下调，Caspase-1表达上调，RPE细胞呈现焦亡表型，提示lncRNA AL591030.1可能通过miR-130a促进RPE细胞焦亡。在此基础上，我们拟采用RIP、双荧光素酶报告基因实验及挽救实验等手段，阐明外泌体源lncRNA AL591030.1靶向miR-130a介导的信号通路激活Caspase-1促进RPE细胞焦亡进而影响DR发病的功能与机制，为DR提供新研究思路和潜在治疗手段。

Diabetic retinopathy (DR) is a highly blinding eye disease. The pyrolysis of human retinal pigment epithelium (RPE) cells promotes the onset of DR, while exosomes are closely related to pyrolysis of cells. However, the underlying mechanisms remains unclear. We treated RPE cells with high glucose to establish the DR cell models. By which, we found that miR-130a-mediated signaling pathway could inhibit the pyroptosis of RPE cells. Moreover, RPE cells of DR model secreted upregulated exosomes, which is enriched of lncRNA AL591030.1. The exosome-derived lncRNA AL591030.1 may interact with miR-130a. Furthermore, overexpression of lncRNA AL591030.1 inhibited the expression of miR-130a, thereby promoting caspase-1 expression, and resulted in pyroptosis of RPE cells. Basis on these findings, we proposed this project that intend to use RIP, luciferase reporter gene experiment, and rescue experiment etc. to illustrate the function and mechanisms of exosome-derived lncRNA AL591030.1 in that activation of caspase-1 by targeting miR-130a-mediated signal pathway, leading to the pyroptosis of RPE cells. Our work will provide novel insights into the pathogenesis of DR and potential treatments for DR.