April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Photoreceptor sensitivity to oxidative stress can by regulated by non-redundant roles of PGC-1α and PGC-1β
Author Affiliations & Notes
  • Carolina Elizabeth Abrahan
    Ophthalmology, University of Florida, Gainesville, FL
  • John D Ash
    Ophthalmology, University of Florida, Gainesville, FL
  • Footnotes
    Commercial Relationships Carolina Abrahan, None; John Ash, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5756. doi:
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      Carolina Elizabeth Abrahan, John D Ash; Photoreceptor sensitivity to oxidative stress can by regulated by non-redundant roles of PGC-1α and PGC-1β. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5756.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Inherited retinal degenerations are often the result of photoreceptor cell death. While there are numerous pathways to induce photoreceptor death, a common mechanism of death is oxidative stress. Mitochondria are known to play a key role in production of reactive oxygen species (ROS), and are known to be damaged in disease. However, mitochondria are also a major source of ROS detoxification enzymes and energy. Both are needed for cell survival. Our purpose was to determine whether peroxisome proliferator-activated receptor gamma coactivator-alpha (PGC-1 α) and beta (PGC-1 β), key regulators of mitochondrial biogenesis, play a role in regulating retina cell survival under oxidative stress.

Methods: We used electroretinogram (ERG) measurements of retinal function and spectral domain optical coherence tomography (SD-OCT) measurements of retinal structure to determine whether germ line knockout of PGC-1α or retina specific knock-out of PGC-1β altered sensitivity to damaging light. We exposed 2-4 months old knock-out mice to damaging light (1-2 mice per cage illuminated with white LED; 1000-1200lux; 4hours). We measured retinal function and structure 5-7 days after light damage.

Results: Under normal lighting conditions, PGC-1α and PGC-1β knock-out mice had normal light responses by ERG and normal retina morphology by SD-OCT imaging. Both lines of knockout mice were healthy, but the germline knockout of PGC-1α resulted in small and hyperactive mice. Light damage reduced retinal function and thickness in both PGC-1α and wild type mice, but PGC-1α knock-out mice were less susceptible to light damage than wild type mice. In contrast, PGC-1β knock-out mice were more susceptible to light damage than wild type mice.

Conclusions: Our data show that neither loss of PGC-1α or PGC-1β caused retinal degeneration suggesting that either these proteins are not necessary for normal retinal function or that they have a redundant function. Interestingly, the whole body knockout of PGC-1α in mice induces protection against light damage whereas the retina-specific knockout of PGC-1β increases retinal susceptibility to light damage. These results suggest that the two proteins may have unique functions in retinal physiology. Alternatively, it is possible that the hyperactivity of the germline PGC-1α knockout mice plays a role in protection.

Keywords: 615 neuroprotection • 600 mitochondria • 695 retinal degenerations: cell biology  

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