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PGC1a rescue retinal pigment epithelial cells from oxidative damage: implication for age‐related macular degeneration
Author(s) -
Khadka Arogya,
Iacovelli Jared,
SaintGeniez Magali
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.148.4
Subject(s) - sod2 , macular degeneration , retinal pigment epithelium , oxidative phosphorylation , population , oxidative stress , drusen , biology , retinal , reactive oxygen species , chemistry , microbiology and biotechnology , superoxide dismutase , biochemistry , medicine , environmental health , ophthalmology
Age‐related macular degeneration (AMD) is the leading cause of blindness in the elderly population of industrialized countries. AMD is thought to occur, at least in part, from oxidative damage to the retinal pigment epithelium (RPE). Thus, enhancement of the anti‐oxidant response of RPE is an attractive treatment for AMD. The transcriptional co‐activator, peroxisome proliferator‐activated receptor‐gamma coactivator 1α (PGC‐1α), is powerful mediator of cellular oxidative metabolism, and anti‐oxidant response. Our previous studies showed that PGC‐1α controls RPE oxidative metabolism and maturation. Here we examine the ability of PGC‐1α to protect RPE from oxidative damage. Overexpression of PGC‐1a in RPE strongly induced genes of antioxidant enzymes including CAT, GPX1, PRDX3, SOD1, SOD2, and TXN2. The cytotoxic effect of clinically relevant oxidants including H 2 O 2 (released during photoreceptor outer segment phagocytosis) and hydroquinone (cigarette smoke oxidant) was evaluated. Our results demonstrate that both H 2 O 2 andhydroquinone lead to generation of reactive oxidant species (ROS) and necrosis in RPE in a time‐ and dose‐dependent manner. Importantly, this oxidant‐mediated cytotoxic effect was dramatically reduced by PGC‐1α overexpression. These results demonstrates that PGC‐1α not only controls RPE metabolism but also protect RPE cells from oxidative damage via the induction of a large panel of anti‐oxidant enzymes. Strategies aimed at increasing PGC‐1α expression and/or function may be beneficial for the treatment of retinal degenerative disorders such as AMD.