早期糖尿病视网膜致病特异性miRNA筛查与基因调控研究

项目名称： 早期糖尿病视网膜致病特异性miRNA筛查与基因调控研究

项目编号： No.81200689

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 于旭辉

作者单位： 哈尔滨医科大学

项目金额： 23万元

中文摘要： 早期糖尿病视网膜病变(DR)的神经元、神经胶质细胞和微血管之间，存在复杂的网络调控机制，其分子病理扳机点至今尚未确定，转录后miRNA调控在其中发挥举足轻重的作用。课题组拟入组正常个体、早期糖尿病无DR个体以及早期DR个体，分别获取视网膜进行总RNA提取，应用人miRNA芯片杂交，分别构建miRNA表达谱，通过比对差异分析，选择差异性最显著的候选miRNA，用Real-time PCR技术进行定量，应用miRNA 原位杂交 (ISH) 技术进行细胞定位，筛选早期DR表达的视网膜特异性miRNA ，将候选miRNA 体外在细胞水平上给予干预性表达调控，进行功能分析研究，明确miRNA 的靶基因序列，探讨miRNA的基因调控机制。并将可能作为生物标记物的miRNA进行糖尿病非DR个体和DR个体外周血中miRNA的表达监测，以期获取超早期DR诊断的生物学标记物。

中文关键词： 糖尿病视网膜病变；超早期筛查；miRNA；生物标记物；

英文摘要： Diabetic retinopathy (DR) is one of the leading causes of blindness. There remains a critical need to better understand the underlying disease mechanisms responsible for DR in order to develop new and improved therapeutic strategies for this chronic condition. DR is a result of multiple pathogenetic processes caused by hyperglycemia and abnormalities of insulin signaling pathways , leading to retinal microvascular defects and neuroretinal dysfunction and degeneration. Although significant progress has been made, molecular mechanisms underlying the pathogenesis of DR are still not fully understood;current treatments have resulted in only a partial reduction in this risk, and the management of these conditions remains advancing need for those with diabetes. New insights have come from a novel family of endogenous, small (～22 nucleotides), single stranded, noncoding RNA molecules known as microRNAs (miRNAs) as developmental regulators. These molecules, only identified in humans in the last decade, modulate physiological and pathological processes by the posttranscriptional inhibition of gene expression. Many excellent performance has demonstrated miRNAs play important roles in diabetes and its complications, regulating multiple biological pathways closely related to DR . Recently, several studies have been re

英文关键词： Diabetic Retinopathy；early screen；miRNA；biomarker；