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PGC-1α determines light damage susceptibility of the murine retina

Egger, A. and Samardzija, M. and Sothilingam, V. and Tanimoto, N. and Lange, C. and Salatino, S. and Fang, L. and Garcia-Garrido, M. and Beck, S. and Okoniewski, M. J. and Neutzner, A. and Seeliger, M. W. and Grimm, C. and Handschin, C.. (2012) PGC-1α determines light damage susceptibility of the murine retina. PLoS ONE, Vol. 7, H. 2 , e31272.

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Official URL: http://edoc.unibas.ch/dok/A6002509

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Abstract

The peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1) proteins are key regulators of cellular bioenergetics and are accordingly expressed in tissues with a high energetic demand. For example, PGC-1α and PGC-1β control organ function of brown adipose tissue, heart, brain, liver and skeletal muscle. Surprisingly, despite their prominent role in the control of mitochondrial biogenesis and oxidative metabolism, expression and function of the PGC-1 coactivators in the retina, an organ with one of the highest energy demands per tissue weight, are completely unknown. Moreover, the molecular mechanisms that coordinate energy production with repair processes in the damaged retina remain enigmatic. In the present study, we thus investigated the expression and function of the PGC-1 coactivators in the healthy and the damaged retina. We show that PGC-1α and PGC-1β are found at high levels in different structures of the mouse retina, most prominently in the photoreceptors. Furthermore, PGC-1α knockout mice suffer from a striking deterioration in retinal morphology and function upon detrimental light exposure. Gene expression studies revealed dysregulation of all major pathways involved in retinal damage and apoptosis, repair and renewal in the PGC-1α knockouts. The light-induced increase in apoptosis in vivo in the absence of PGC-1α was substantiated in vitro, where overexpression of PGC-1α evoked strong anti-apoptotic effects. Finally, we found that retinal levels of PGC-1 expression are reduced in different mouse models for retinitis pigmentosa. We demonstrate that PGC-1α is a central coordinator of energy production and, importantly, all of the major processes involved in retinal damage and subsequent repair. Together with the observed dysregulation of PGC-1α and PGC-1β in retinitis pigmentosa mouse models, these findings thus imply that PGC-1α might be an attractive target for therapeutic approaches aimed at retinal degeneration diseases.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Ocular Pharmacology and Physiology (Neutzner/Meyer)
UniBasel Contributors:Neutzner, Albert
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Public Library of Science
e-ISSN:1932-6203
Note:Variant title: PGC-1alpha determines light damage susceptibility of the murine retina -- Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:31 Aug 2018 06:39
Deposited On:14 Sep 2012 07:16

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