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.
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