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Int. J. Mol. Sci. 2018, 19(8), 2317; https://doi.org/10.3390/ijms19082317

PGC-1α Protects RPE Cells of the Aging Retina against Oxidative Stress-Induced Degeneration through the Regulation of Senescence and Mitochondrial Quality Control. The Significance for AMD Pathogenesis

1
Department of Ophthalmology, University of Eastern Finland, 70211 Kuopio, Finland
2
Department of Ophthalmology, Kuopio University Hospital, 70029 Kuopio, Finland
3
Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland
4
Department of General and Colorectal Surgery, Medical University of Lodz, Pl. Hallera 1, 90-647 Lodz, Poland
5
Department of Orthodontics, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland
*
Author to whom correspondence should be addressed.
Received: 12 June 2018 / Revised: 18 July 2018 / Accepted: 5 August 2018 / Published: 7 August 2018
(This article belongs to the Special Issue Molecular Biology of Age-Related Macular Degeneration (AMD))
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Abstract

PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is a transcriptional coactivator of many genes involved in energy management and mitochondrial biogenesis. PGC-1α expression is associated with cellular senescence, organismal aging, and many age-related diseases, including AMD (age-related macular degeneration), an important global issue concerning vision loss. We and others have developed a model of AMD pathogenesis, in which stress-induced senescence of retinal pigment epithelium (RPE) cells leads to AMD-related pathological changes. PGC-1α can decrease oxidative stress, a key factor of AMD pathogenesis related to senescence, through upregulation of antioxidant enzymes and DNA damage response. PGC-1α is an important regulator of VEGF (vascular endothelial growth factor), which is targeted in the therapy of wet AMD, the most devastating form of AMD. Dysfunction of mitochondria induces cellular senescence associated with AMD pathogenesis. PGC-1α can improve mitochondrial biogenesis and negatively regulate senescence, although this function of PGC-1α in AMD needs further studies. Post-translational modifications of PGC-1α by AMPK (AMP kinase) and SIRT1 (sirtuin 1) are crucial for its activation and important in AMD pathogenesis. View Full-Text
Keywords: PGC-1α; age-related macular degeneration; AMD; senescence; mitochondrial quality control; mitochondria; oxidative stress PGC-1α; age-related macular degeneration; AMD; senescence; mitochondrial quality control; mitochondria; oxidative stress
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Kaarniranta, K.; Kajdanek, J.; Morawiec, J.; Pawlowska, E.; Blasiak, J. PGC-1α Protects RPE Cells of the Aging Retina against Oxidative Stress-Induced Degeneration through the Regulation of Senescence and Mitochondrial Quality Control. The Significance for AMD Pathogenesis. Int. J. Mol. Sci. 2018, 19, 2317.

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