title: Peroxisome proliferator-activated receptor α 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 α (PPARα) agonist, has robust therapeutic effects on diabetic retinopathy in type 2 diabetic patients. We evaluated the protective effect of PPARα against pericyte loss in diabetic retinopathy. In streptozotocin-induced diabetic mice, fenofibrate treatment significantly ameliorated retinal acellular capillary formation and pericyte loss. In contrast, PPARα(-/-) mice with diabetes developed more severe retinal acellular capillary formation and pericyte dropout, compared with diabetic wild-type mice. Furthermore, PPARα knockout abolished the protective effect of fenofibrate against diabetes-induced retinal pericyte loss. In cultured primary human retinal capillary pericytes, activation and expression of PPARα 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-κB activation. Furthermore, activation and expression of PPARα both attenuated the oxidant-induced suppression of mitochondrial O2 consumption in human retinal capillary pericytes. Primary retinal pericytes from PPARα(-/-) mice displayed more apoptosis, compared with those from wild-type mice under the same oxidative stress. These findings identified a protective effect of PPARα on retinal pericytes, a novel function of endogenous PPARα in the retina.
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China; Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors.forename: Lexi
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors.forename: Rui
authors.initials: R
authors.lastname: Cheng
authors.affiliation: Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia.
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Jenkins
authors.affiliation: National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Keech
authors.affiliation: Free Radical Biology and Aging Research Program, Medical Research Foundation, Oklahoma City, Oklahoma.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Humphries
authors.affiliation: Department of Ophthalmology, Dean McGee Eye Institute, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; Department of Ophthalmology, Dean McGee Eye Institute, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Elliott
authors.affiliation: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China. Electronic address: xbxia21@163.com.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Electronic address: jian-xing-ma@ouhsc.edu.
authors.forename: Jian-Xing
authors.initials: JX
authors.lastname: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D011345:Fenofibrate / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D020286:Pericytes / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D047493:PPAR alpha; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D011345:Fenofibrate
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