Peroxisome proliferator-activated receptor ? protects capillary pericytes in the retina.

ABSTRACT: Pericyte degeneration is an early event in diabetic retinopathy and plays an important role in progression of diabetic retinopathy. Clinical studies have shown that fenofibrate, a peroxisome proliferator-activated receptor ? (PPAR?) agonist, has robust therapeutic effects on diabetic retinopathy in type 2 diabetic patients. We evaluated the protective effect of PPAR? against pericyte loss in diabetic retinopathy. In streptozotocin-induced diabetic mice, fenofibrate treatment significantly ameliorated retinal acellular capillary formation and pericyte loss. In contrast, PPAR?(-/-) mice with diabetes developed more severe retinal acellular capillary formation and pericyte dropout, compared with diabetic wild-type mice. Furthermore, PPAR? knockout abolished the protective effect of fenofibrate against diabetes-induced retinal pericyte loss. In cultured primary human retinal capillary pericytes, activation and expression of PPAR? both significantly reduced oxidative stress-induced apoptosis, decreased reactive oxygen species production, and down-regulated NAD(P)H oxidase 4 expression through blockade of NF-?B activation. Furthermore, activation and expression of PPAR? both attenuated the oxidant-induced suppression of mitochondrial O2 consumption in human retinal capillary pericytes. Primary retinal pericytes from PPAR?(-/-) mice displayed more apoptosis, compared with those from wild-type mice under the same oxidative stress. These findings identified a protective effect of PPAR? on retinal pericytes, a novel function of endogenous PPAR? in the retina.

SUBMITTER: Ding L 

PROVIDER: S-EPMC4188867 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature