July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Channelrhodopsin mediated retinal ganglion cell responses in the living macaque
Author Affiliations & Notes
  • Juliette E McGregor
    Center for Visual Science, University of Rochester, Rochester, New York, United States
  • Tyler Godat
    Center for Visual Science, University of Rochester, Rochester, New York, United States
    Institute of Optics, University of Rochester, Rochester, New York, United States
  • Keith Parkins
    Center for Visual Science, University of Rochester, Rochester, New York, United States
  • Jennifer Strazzeri
    Center for Visual Science, University of Rochester, Rochester, New York, United States
    Flaum Eye Institute, University of Rochester, Rochester, New York, United States
  • David R Williams
    Center for Visual Science, University of Rochester, Rochester, New York, United States
    Institute of Optics, University of Rochester, Rochester, New York, United States
  • William H Merigan
    Center for Visual Science, University of Rochester, Rochester, New York, United States
    Flaum Eye Institute, University of Rochester, Rochester, New York, United States
  • Footnotes
    Commercial Relationships   Juliette McGregor, None; Tyler Godat, None; Keith Parkins, None; Jennifer Strazzeri, None; David Williams, Canon Inc (F), University of Rochester (P); William Merigan, None
  • Footnotes
    Support  R01 EY021166, U01EY025497, Beckman-Argyros Award
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2589. doi:
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    • Get Citation

      Juliette E McGregor, Tyler Godat, Keith Parkins, Jennifer Strazzeri, David R Williams, William H Merigan; Channelrhodopsin mediated retinal ganglion cell responses in the living macaque. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2589.

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

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Abstract

Purpose : Optogenetics offers the prospect of vision restoration following photoreceptor degeneration by conferring light sensitivity to postreceptoral retinal neurons. Channelrhodopsin mediated activity in primate retinal ganglion cells (RGCs) has been demonstrated in ex-vivo preparations but not in the living primate. We assess channelrhodopsin mediated responses in the intact macaque by optically recording from RGCs expressing both a channelrhodopsin (ChrimsonR) and a calcium indicator (GCaMP6s).

Methods : AAV2-CAG-G-CaMP6s and AAV2-CAG-ChrimsonR-tdTomato were co-injected into the vitreous of two normal male macaques (M. fascicularis). Adaptive optics scanning light ophthalmoscopy (AOSLO) of GCaMP fluorescence (ex. 488 nm, em. 520/35 nm) was performed while 561 nm drifting gratings were presented at 0.2Hz and 1-5 cycles/deg. Stimuli were stabilized to compensate for the effects of eye motion. Recordings were made at 6, 7, and 19 weeks following injection. Response amplitude and phase were quantified by temporal Fourier analysis.

Results : GCaMP6s and ChrimsonR were co-expressed in RGCs in a ring around the foveal center. We demonstrated that RGCs could be driven in either of two ways, either through the normal photoreceptor pathway or through direct stimulation of ChrimsonR in the RGCs themselves. These pathways can be distinguished using the lateral displacement of the RGCs from the photoreceptors that drive them. The possibility that stray light scattering on foveal photoreceptors generated the response when the stimulus was delivered directly to the RGCs was ruled out by the spatial variation across the RGC array of the temporal phase of RGC responses.

Conclusions : We observe ChrimsonR mediated calcium activity in the foveal RGCs of living macaques. While optogenetic vision restoration has been successfully achieved in the living mouse, demonstrating this in primates is an important step toward deployment in humans. Non-invasive optical recording from RCGs allows longitudinal monitoring and direct observation of vision restoration in the retinal circuitry of the living primate.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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