TY - JOUR
T1 - Peroxisome proliferatore activated receptor a protects capillary pericytes in the retina
AU - Ding, Lexi
AU - Cheng, Rui
AU - Hu, Yang
AU - Takahashi, Yusuke
AU - Jenkins, Alicia J.
AU - Keech, Anthony C.
AU - Humphries, Kenneth M.
AU - Gu, Xiaowu
AU - Elliott, Michael H.
AU - Xia, Xiaobo
AU - May, Jian Xing
N1 - Publisher Copyright:
Copyright © 2014 American Society for Investigative Pathology.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajpath.2014.06.021
DO - 10.1016/j.ajpath.2014.06.021
M3 - Article
C2 - 25108226
AN - SCOPUS:84922439273
SN - 0002-9440
VL - 184
SP - 2709
EP - 2720
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 10
ER -