June 2017
Volume 58, Issue 8
ARVO Annual Meeting Abstract  |   June 2017
A non-redundant role for PGC-1β in retinal homeostasis and photoreceptor resistance to oxidative stress induced by light exposure
Author Affiliations & Notes
  • Casey J Keuthan
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Cassidy M Chason
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • John D Ash
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Footnotes
    Commercial Relationships   Casey Keuthan, None; Cassidy Chason, None; John Ash, None
  • Footnotes
    Support  Funding support to JDA includes NIH R01EY016459-11, Foundation Fighting Blindness, and an unrestricted departmental grant from Research to Prevent Blindness, Inc. Training support to CJK includes NIH T32EY007132.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3016. doi:https://doi.org/
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      Casey J Keuthan, Cassidy M Chason, John D Ash; A non-redundant role for PGC-1β in retinal homeostasis and photoreceptor resistance to oxidative stress induced by light exposure. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3016. doi: https://doi.org/.

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

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Purpose : The peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) family members are considered master regulators of mitochondrial biogenesis and metabolism. Although PGC-1 has been studied in a variety of high-energy tissues, the non-redundancies between the individual PGC-1α and PGC-1β isoforms are not well established. Moreover, the function of PGC-1β in the retina remains largely unknown. This work aimed to further elucidate the role of PGC-1β in photoreceptor protection during aging and in light stress conditions.

Methods : Chx10Cre;PGC-1βf/f mice are conditional knockouts (cKO) of PGC-1β in retinal neurons and Müller glial cells. Littermates not expressing Cre were used as controls. All animals were reared in dim light conditions (<100 lux). For light stress, mice were exposed to light (400 lux or greater). Spectral Domain Optical Coherence Tomography (SD-OCT) was used to study retinal morphology, and retinal function was measured by electroretinography (ERG). Retinas were collected for quantitative RT-PCR (qRT-PCR) to measure mRNA expression. All procedures with animals were conducted in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.

Results : In dim light, young adult (2 months) PGC-1β cKO mice had normal retinas, suggesting these mice had normal retinal development. As cKO mice aged, ONL thinning was observed around 6-9 months by OCT. Around 15 months of age, there was a decrease in cardiolipin synthase and acetyl-CoA carboxylase expression, but no significant changes were observed in oxidative stress markers or mitochondrial-related genes involved in oxidative phosphorylation. Interestingly, young cKO mice were more sensitive to light stress, since they were damaged by light levels that are normally non-damaging in wild-type mice. This included significant outer nuclear layer (ONL) thinning and reduced ERG a-wave amplitudes. Differences in PGC-1α mRNA expression were not obvious in light stressed or aged mice.

Conclusions : Our data suggest a critical role for PGC-1β in photoreceptor survival with age and protection from light stress. This role could not be compensated by PGC-1α. We hypothesize that PGC-1β plays a non-redundant role in mitigating metabolic stress of aging and light-induced oxidative damage. This role may involve maintenance of lipid synthesis and other mitochondrial-related processes.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.


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