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Jared Iacovelli, Zoltan Arany, Magali Saint-Geniez; PGC-1 isoforms regulate photoreceptor response to photo-oxidative stress: relevance to retinal degenerative diseases. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1796.
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© ARVO (1962-2015); The Authors (2016-present)
Photoreceptors (PRs) are exposed to high oxidative stress due to their high oxygen consumption, high levels of light irradiation, and abundance of readily oxidized poly-unsaturated fatty acids in outer segments. This study examines the expression of peroxisome proliferator-activated receptor-gamma coactivator 1 α and β (PGC-1α/β), critical regulators of cellular metabolism and antioxidant response, in retina and their role in PR oxidative stress response in vitro.
Expression of PGC-1α/β in mouse retina was studied by in situ hybridization and qPCR. 661w, cone PR-like cells, were exposed to bright white fluorescent light to induce photo-oxidative stress. Oxidative stress and reactive oxygen species (ROS) were measured by CM-H2DCFDA fluorescence. Cell death was analyzed by LDH release. PGC-1α/β and selected anti-oxidant enzyme gene expression was analyzed by qPCR. PGC-1α/β expression was modulated using adenoviral overexpression vectors and RNAi mediated knock-down.
PGC-1α and β expression increased 52 and 311-fold, respectively, during post-natal retinal development in mice, coinciding with increased mitochondrial gene expression. Short exposure to photo-oxidative stress significantly increased ROS (p<0.05) and prolonged exposure lead to cell death (p<0.01). PGC-1α expression and antioxidant gene expression increased in response to photo-oxidative stress. RNAi knock-down of PGC1α and β increased cell death 3-fold.
Post-natal induction of PGC-1α/β expression suggests a role in regulating the mitochondria burst associated with PR maturation. The increased light-induced cell death following PGC-1α/β knock-down implies a role for PGC-1 isoforms in PR antioxidant response.
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