September 2023
Volume 23, Issue 11
Open Access
Optica Fall Vision Meeting Abstract  |   September 2023
Contributed Session I: Foveal RGCs develop abnormal calcium clearance weeks after photoreceptor ablation
Author Affiliations
  • Zhengyang Xu
    Institute of Optics, University of Rochester, Rochester, New York, UNITED STATES
  • Karteek Kunala
    Center for Visual Science, University of Rochester Medical Center, Rochester, New York, UNITED STATES
  • Peter Murphy
    Institute of Optics, University of Rochester, Rochester, New York, UNITED STATES
  • Edith Koo
    Institute of Optics, University of Rochester, Rochester, New York, UNITED STATES
  • Teresa Puthussery
    Herbert Wertheim School of Optometry & Vision Science, University of California Berkeley, Berkeley, California, UNITED STATES
    Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, UNITED STATES
  • Juliette E. McGregor
    Center for Visual Science, University of Rochester Medical Center, Rochester, New York, UNITED STATES
    Flaum Eye Institute, University of Rochester Medical Center, Rochester, New York, UNITED STATES
Journal of Vision September 2023, Vol.23, 11. doi:https://doi.org/10.1167/jov.23.11.11
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      Zhengyang Xu, Karteek Kunala, Peter Murphy, Edith Koo, Teresa Puthussery, Juliette E. McGregor; Contributed Session I: Foveal RGCs develop abnormal calcium clearance weeks after photoreceptor ablation. Journal of Vision 2023;23(11):11. https://doi.org/10.1167/jov.23.11.11.

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

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Abstract

Vision restoration therapies aim to restore light sensitivity to the retina following photoreceptor (PR) degeneration. Physiological changes in retinal ganglion cells (RGCs) have been reported in rodent models of PR loss but this has not been investigated in primates. By expressing both a calcium indicator (GCaMP6s) and an optogenetic actuator (ChrimsonR) in foveal RGCs of a macaque, we reactivate RGCs and assess activity in the weeks and years following PR loss. Cones were ablated with an ultrafast laser delivered through an adaptive optics scanning light ophthalmoscope (AOSLO). A 0.5 s optogenetic stimulus (1 mW, 640 nm) was delivered to the deafferented RGCs, and GCaMP fluorescence was recorded for 90 s. The calcium response was collected with AOSLO over 10 weeks and the signal decay was fitted with an exponential model. Optogenetic responses in RGCs persisted over 2 years following PR ablation. The mean time to peak calcium response was stable in deafferented RGCs over the 10 weeks (paired t-test, p<0.001), while the mean decay constant of the calcium response decreased 2.1 fold (2.5±0.5 s to 1.2±0.2 s SD) in the 8 weeks post PR ablation. The presence of optogenetic responses 2 years after PR loss and the stable rise time is promising for vision restoration therapies with RGCs. However, the 2-fold reduction in the decay constant of the calcium response suggests that restored activity may be impacted by physiological changes in the inner retina weeks after PR loss.

Footnotes
 Funding: Funding: Funding from the AGI initiative NIH U24 EY033275, CVS core support from NIH P30 EY0001319 An unrestricted grant to the Flaum Eye Institute from Research to Prevent Blindness and the Steven. E. Feldon Scholarship from the Flaum Eye Institute
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