Müller细胞来源的外泌体携带LncPILRB激活小胶质细胞内NLRP3通路介导糖尿病视网膜神经损伤的作用及机制研究

糖尿病视网膜病变（DR）是主要的致盲眼病，炎性神经损伤是其重要病理特征。外泌体作为细胞间信号传导媒介，其介导的炎症机制有待进一步阐明。我们前期研究发现增殖性DR患者和糖尿病小鼠视网膜内小胶质细胞中miR-133b下调；miR-133b可抑制NLRP3表达；高糖刺激后Müller细胞分泌的外泌体测序显示LncPILRB上调，LncPILRB与miR-133b有多结合位点。据此提出假说：DR视网膜müller细胞分泌的外泌体携带LncPILRB，竞争性抑制miR-133b，进而激活小胶质细胞内NLRP3，介导视网膜神经损伤。围绕该假说，本项目拟通过细胞和动物实验，明确LncPILRB在DR神经损伤中的角色，验证LncPILRB/miR-133b/NLRP3信号通路，并探讨外泌体在müller细胞-小胶质细胞间传输LncPILRB信号的作用，为探索DR的神经损伤机制和干预靶点提供新思路。

Diabetic retinopathy (DR) is one of the leading courses of vision loss. DR is characterized by para-inflammation-induced retinal neuropathy. Exosome, as extracellular vesicle, is emerging as a key mediator of intercellular communication, and its role in mediating retinal inflammation is unknown. Our previous work suggested that miR-133b was downregulated in PDR vitreous and retinal microglia cells from diabetic mice. MiR-133b was identified as the suppressor of NLRP3 mRNA. Further, next-generation-sequencing indicated that exosomes derived from müller cells were enriched of LncPILRB, which has multiple binding sites for miR-133b. Taken together we assume that exosome is a crucial vehicle for intercellular transportation of LncPILRB, which activates NLRP3 by sponging miR-133b. This project is to explore the role of LncPILRB in diabetic neuropathy, the LncPILRB /miR-133b/NLRP3 pathway, and the transportation of LncPILRB by exosomes between müller cells and microglia. This work would shed light the DR pathogenesis and provide novel targets for treatment of DR.