July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Signals triggering electrophysical remodeling in retinal degeneration
Author Affiliations & Notes
  • Richard H Kramer
    Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, United States
  • Footnotes
    Commercial Relationships   Richard Kramer, Photoswitch Biosciences (P), Photoswitch Biosciences (I)
  • Footnotes
    Support  NIH Grant R01EY024334
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2842. doi:
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    • Get Citation

      Richard H Kramer; Signals triggering electrophysical remodeling in retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2842.

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

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Presentation Description : Light responses are initiated in photoreceptors, processed by interneurons, and synaptically transmitted to retinal ganglion cells (RGCs), which send information to the brain. Retinitis pigmentosa (RP) is a blinding disease caused by photoreceptor degeneration, depriving downstream neurons of light-sensitive input. In addition, photoreceptor degeneration triggers hyperactive firing of RGCs that obscures light responses initiated by surviving photoreceptors. I will present results showing that retinoic acid (RA), signaling through its receptor (RAR), is the trigger for hyperactivity. A genetically-encoded fluorescent reporter shows elevated RAR signaling in degenerated retinas from murine models of RP. Enhancing RAR signaling in healthy retinas mimics the pathophysiology of degenerating retinas. Drug inhibition of RAR reduces hyperactivity in degenerating retinas and unmasks light responses in RGCs. Gene therapy inhibition of RAR increases innate and learned light-elicited behaviors in vision-impaired mice. Identification of RAR as the trigger for hyperactivity presents a degeneration-dependent therapeutic target for enhancing low-level vision in RP and other blinding disorders.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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