A NOVEL FUNCTION OF FENOFIBRATE IN DIABETIC RETINOPATHY IN THE TYPE 1 DIABETES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 糖尿病视网膜病变是糖尿病常见的血管并发症，也是工作年龄人群致盲的主要原因。视网膜血管渗漏和视网膜炎症引起的视网膜新生血管和糖尿病性黄斑水肿是糖尿病性视网膜病变视力下降的主要病理特征。虽然抗VEGF试剂的最新进展显示了令人鼓舞的结果，但糖尿病视网膜病变仍然是工业化国家失明的主要原因。非诺贝特，临床上可用于治疗血脂异常超过30年，是特别有效的改善血脂高，在代谢综合征和2型糖尿病的人的常见配置文件，并减少一些心血管事件。最近两项大型前瞻性安慰剂对照临床试验证实了非诺贝特对2型糖尿病DR的保护作用。 尽管有令人兴奋的临床发现，但仍存在一些未回答的问题。非诺贝特对1型糖尿病视网膜病变有效吗？ 非诺贝特是否直接影响视网膜血管渗漏、炎症和NV，其潜在的作用机制是什么？ 这个受资助的COBRA试点项目旨在研究这些重要问题。目前，本项目确定了PPAR α激活对1型糖尿病视网膜病变的新的治疗作用，并致力于揭示非诺贝特抗糖尿病视网膜病变的潜在机制。本项目将为糖尿病并发症的发病机制提供新的见解，并将揭示糖尿病视网膜病变药物干预的新靶点。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Diabetic retinopathy is a common vascular complication of diabetes mellitus and a leading cause of blindness in the working age population. Retinal neovascularization and diabetic macular edema caused by retinal vascular leakage and retinal inflammation are the major pathological features responsible for vision loss in diabetic retinopathy. Although recent progress in anti-VEGF reagents has displayed encouraging outcomes, diabetic retinopathy remains a major cause of blindness in the industrialized countries. Fenofibrate, available clinically over 30 years for the treatment of dyslipidemia, is particularly effective in improving the lipid profile in hypertriglyceridemia, a common profile in people with the metabolic syndrome and type 2 diabetes, and for reducing some cardiovascular events. Two recent large prospective placebo controlled clinical trials demonstrate protective effect of fenofibrate against DR in type 2 diabetes. Despite the exciting clinical findings, several unanswered questions remain. Is fenofibrate effective on diabetic retinopathy in type 1 diabetes? Does fenofibrate directly impact on retinal vascular leakage, inflammation and NV, and what is its underlying mechanism of action? This funded COBRA pilot project is designed to examine these important questions. Currently, this project identify a novel therapeutic role of PPAR alpha activation for the diabetic retinopathy in type 1 diabetic retinopathy, and are working on reveal the underlying mechanism of fenofibrate against diabetic retinopathy. This project will provide new insights into the pathogenesis of diabetic complications, and will reveal a new target for drug intervention of diabetic retinopathy.