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 proliferatoreactivated 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 a cellular 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 stresseinduced apoptosis, decreased reactive oxygen species production, and down-regulated NAD(P)H oxidase 4 expression through blockade of NF-κ B activation. Furthermore, activation and expression of PPAR& both attenuated the oxidant-induced suppression of mitochondrial O<>2<> 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.
ASJC Scopus subject areas
- Pathology and Forensic Medicine