Peroxisome proliferator-activated receptor α protects capillary pericytes in the retina

Am J Pathol. 2014 Oct;184(10):2709-20. doi: 10.1016/j.ajpath.2014.06.021. Epub 2014 Aug 7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Capillaries / drug effects
  • Capillaries / metabolism
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Type 2 / chemically induced
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Retinopathy / chemically induced
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / metabolism
  • Disease Models, Animal
  • Fenofibrate / pharmacology*
  • Gene Expression Regulation
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NADPH Oxidases / metabolism
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • PPAR alpha / agonists*
  • PPAR alpha / metabolism
  • Pericytes / drug effects*
  • Pericytes / metabolism
  • Reactive Oxygen Species / metabolism
  • Retina / drug effects
  • Retina / metabolism


  • NF-kappa B
  • PPAR alpha
  • Reactive Oxygen Species
  • NADPH Oxidases
  • Fenofibrate