| First Author | Ding L | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 10 | Pages | 2709-20 |
| PubMed ID | 25108226 | Mgi Jnum | J:216061 |
| Mgi Id | MGI:5607659 | Doi | 10.1016/j.ajpath.2014.06.021 |
| Citation | Ding L, et al. (2014) Peroxisome proliferator-activated receptor alpha protects capillary pericytes in the retina. Am J Pathol 184(10):2709-20 |
| abstractText | 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 alpha (PPARalpha) agonist, has robust therapeutic effects on diabetic retinopathy in type 2 diabetic patients. We evaluated the protective effect of PPARalpha against pericyte loss in diabetic retinopathy. In streptozotocin-induced diabetic mice, fenofibrate treatment significantly ameliorated retinal acellular capillary formation and pericyte loss. In contrast, PPARalpha(-/-) mice with diabetes developed more severe retinal acellular capillary formation and pericyte dropout, compared with diabetic wild-type mice. Furthermore, PPARalpha knockout abolished the protective effect of fenofibrate against diabetes-induced retinal pericyte loss. In cultured primary human retinal capillary pericytes, activation and expression of PPARalpha 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-kappaB activation. Furthermore, activation and expression of PPARalpha both attenuated the oxidant-induced suppression of mitochondrial O2 consumption in human retinal capillary pericytes. Primary retinal pericytes from PPARalpha(-/-) mice displayed more apoptosis, compared with those from wild-type mice under the same oxidative stress. These findings identified a protective effect of PPARalpha on retinal pericytes, a novel function of endogenous PPARalpha in the retina. |
