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PGC-1α Determines Light Damage Susceptibility of the Murine Retina

pmid: 22348062
pmc: PMC3278422
PGC-1α Determines Light Damage Susceptibility of the Murine Retina
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.
- University of Basel Switzerland
- University of Tübingen Germany
- University of Zurich Switzerland
- Zentral und Hochschulbibliothek Luzern Switzerland
- University Hospital of Basel Switzerland
10018 Ophthalmology Clinic, Light, Science, 610 Medicine & health, 10071 Functional Genomics Center Zurich, Apoptosis, 1100 General Agricultural and Biological Sciences, Retina, Mice, 1300 General Biochemistry, Genetics and Molecular Biology, Animals, Photoreceptor Cells, 1000 Multidisciplinary, Wound Healing, Gene Expression Profiling, Q, R, Retinitis, Disease Models, Animal, Medicine, Energy Metabolism, Research Article, Transcription Factors
10018 Ophthalmology Clinic, Light, Science, 610 Medicine & health, 10071 Functional Genomics Center Zurich, Apoptosis, 1100 General Agricultural and Biological Sciences, Retina, Mice, 1300 General Biochemistry, Genetics and Molecular Biology, Animals, Photoreceptor Cells, 1000 Multidisciplinary, Wound Healing, Gene Expression Profiling, Q, R, Retinitis, Disease Models, Animal, Medicine, Energy Metabolism, Research Article, Transcription Factors
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citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).50 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10% visibility views 462 download downloads 11 - 462views11downloads

