June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Network-mediated responses of ON ganglion cells to electric stimulation change over the course of retinal degeneration
Author Affiliations & Notes
  • Jae-Ik Lee
    Department of Ophthalmology, Henry Ford Health System, Detroit, Michigan, United States
  • Shelley I Fried
    Boston VA Healthcare System, Boston, Massachusetts, United States
    Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
  • Maesoon Im
    Department of Ophthalmology, Henry Ford Health System, Detroit, Michigan, United States
    Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Jae-Ik Lee, None; Shelley Fried, None; Maesoon Im, None
  • Footnotes
    Support  Boston VA Healthcare System (1I01RX001667) and NIH/NEI (R01EY023651)
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4180. doi:
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      Jae-Ik Lee, Shelley I Fried, Maesoon Im; Network-mediated responses of ON ganglion cells to electric stimulation change over the course of retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4180.

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

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Abstract

Purpose : Microelectronic retinal prostheses have been used to restore sight in individuals with profound vision loss caused by outer retinal degenerative diseases. Previously, we reported in the healthy retina that some components of electrically-elicited responses in ON types of retinal ganglion cells (RGCs) resemble the corresponding components of visually-elicited responses. However, it is not known whether such similarities persist as the retina degenerates and so here we studied how responses change over the course of time in rd10 mice.

Methods : Cell-attached patch clamp was used to record spikes from RGCs in retinal explants from rd10 mice, a slow degeneration model of retinitis pigmentosa. Alpha RGCs were targeted by their large soma (>20 µm) and classified as ON or OFF by their response to stationary flashes. After classification, a monophasic half-sinusoidal wave (4 ms duration, -100 µA amplitude) was delivered epiretinally to elicit network-mediated responses. Each stimulus was repeated 7 times. We recorded the spiking activity in ON RGCs from retinas at postnatal days 15 (n=9), 31 (n=9) and 60 (n=4).

Results : Network-mediated responses in ON alpha RGCs varied systematically with age. 1) The peak firing rate decreased as retinal degeneration progressed: 148.3±65.2 Hz, 79.2±35.7 Hz (p=0.008) and 17.1±16.2 Hz (p<0.001) at P15, 31 and 60, respectively. 2) The latency at which peak firing occurred increased as degeneration progressed: latencies to peak firing were 161±40 ms, 224±112 ms (p=0.073) and 536±309 ms (p=0.047) at P15, P31 and P60, respectively.

Conclusions : Sharp changes in peak firing rate and latency were observed over the course of degeneration and should be taken into consideration during the development of stimulation strategies that activate the retinal network. Because bipolar cells are thought to remain intact through P60 and beyond, our results suggest that they become less sensitive to activation during degeneration although it is also possible that photoreceptors are more sensitive to stimulation and activated in the wild type retina.

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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