长链非编码RNA-MIAT靶向Müler细胞反应胶质化调控糖尿病性视神经病变的机制研究

糖尿病视网膜病变（Diabetic retinopathy，DR）是世界性主要致盲眼病之一，微血管异常和视神经病变是其重要的病理特征。最近的研究发现，视网膜神经改变甚或早于微血管改变的发生，其病变机制尚不完全清楚。长链非编码RNA（lncRNAs）是一类重要的基因元件，参与调控众多生理和病理过程。我们前期研究发现，lncRNA-MIAT干预影响Müller细胞的活力、增殖和凋亡；动物实验发现MIAT干预影响糖尿病引起的反应胶质化进程。本项目拟构建离体、在体糖尿病模型，分析多个压力和时间点下MIAT的表达规律; 基于MIAT表达干预，明确MIAT调控视神经病变，尤其是视网膜反应胶质化的作用；基于生物信息学和分子生物学技术，阐明MIAT调控视神经病变的分子机制。研究成果有望为防治糖尿病性视神经病变提供新思路。

Diabetic retinopathy (DR) is one of the most common eye diseases characterized by microvascular abnormality and progressive retinal neurodegeneration. Recent studies reveal that retinal neurodegneration precedes microvascular abnormility, but the mechanism is not fully understood. LncRNAs have emerged as novel regulatory components of eukaryotic genomes and key players in numerous physiological and pathological processes. Our previous study has revealed that MIAT konckdown could affect Müller cell viability, apoptosis and proliferation in vitro, and diabetes-induced reactive gliosis in vivo. In this study, we will detect MIAT expression pattern in high glucose-induced cell apoptosis model and diabetic rat model at different time points, clarify the role of MIAT in diabetes-indcued neurodegeration especilly for reactive gliosis through in vitro or in vivo intervention of MIAT expression, and reveal the molecular mechnasim of MIAT-mediated retinal neurodegeration. This study would provide novel insights into the prevention and treatment of diabetes mellitus-induced retinal neurodegeration.