Peroxisome proliferatore activated receptor a protects capillary pericytes in the retina

Lexi Ding, Rui Cheng, Yang Hu, Yusuke Takahashi, Alicia J. Jenkins, Anthony C. Keech, Kenneth M. Humphries, Xiaowu Gu, Michael H. Elliott, Xiaobo Xia, Jian Xing May

Research output: Contribution to journalArticlepeer-review

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 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-&kappa; 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.

Original languageEnglish (US)
Pages (from-to)2709-2720
Number of pages12
JournalAmerican Journal of Pathology
Volume184
Issue number10
DOIs
StatePublished - 2014
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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