April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Feasibility of a Neurotransmitter-based Retinal Prosthesis: Stimulation of Retinal Ganglion Cells in S334-ter-4 Rats with L-Glutamate
Author Affiliations & Notes
  • P. G. Finlayson
    Wayne State University, Detroit, Michigan
  • G. Abrams
    Wayne State University, Detroit, Michigan
  • R. Iezzi
    Wayne State University, Detroit, Michigan
  • Footnotes
    Commercial Relationships  P.G. Finlayson, None; G. Abrams, Patent on neurotransmitter prosthesis, P; R. Iezzi, Patent on neurotransmitter prosthesis, P.
  • Footnotes
    Support  Ligon Research Center of Vision, an Unrestricted Grant from Research to Prevent Blindness, NIH Grant 5R21EY018709
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4743. doi:
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      P. G. Finlayson, G. Abrams, R. Iezzi; Feasibility of a Neurotransmitter-based Retinal Prosthesis: Stimulation of Retinal Ganglion Cells in S334-ter-4 Rats with L-Glutamate. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4743.

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

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Purpose: : To examine the effectiveness of local glutamate micro-application in exciting retinal ganglion cells (RGCs) in an animal model of retinitis pigmentosa (RP) for the development of a neurotransmitter-based retinal prosthesis.

Methods: : Reponses were examined in postnatal (P) day 60 to 280 S334-ter line 4 rats. Following enzymatic vitrectomy, flattened eyecup preparations were used to record extracellular RGC activity using glass micropipettes. Responses to light and local pressure ejection of glutamate from micropipettes were examined.

Results: : Local exogenous application of glutamate (2 mM) effectively excited RGCs in most retinas [P60-100 (7/8, with 1 RGC exhibiting suppression only), P180-220 (17/32), and P240-280 (6/6)]. RGC responses to exogenous application of glutamate could be linearly related to the duration of ejection. The excitation elicited by glutamate in a few (7) RGCs exhibited a prolonged period (many seconds) of excitation.The range of RGC response latencies to glutamate was 31 to 493 ms (mean ± S.E.: 239 ± 27ms, n = 25). Glutamate application evoked an initial suppression followed by excitation in 5 spontaneously active RGCs. The latency to the onset of this suppression was also highly variable, ranging from 16 to 400 ms. Mean spontaneous RGC discharge rates (n = 69) in retinas from S334-ter-4 rats were also examined in three age groups P60-100 (n = 9), P180-220 (n = 52) and P240-280 (n = 8). Rates did not differ significantly (ANOVA: p = 0.3) between groups [P60-P100 (9.8 ± 3.6 spikes/s), P180-220 (4.5 ± 10.4) and P240-280 (3.0 ± 7.3)]. However, the proportion of RGCs with rates < 1 spikes/s increased from 33% at P60-100, to 68% at P180-220 and 75% at P240-280.

Conclusions: : RGCs retain glutamate excitability even in late stages of retinal degeneration. RGCs rarely exhibited high spontaneous discharge activity, or loss of excitability in degenerated retinas. Local application of L-glutamate was efficacious in stimulating RGCs, and responses could be linearly modulated according to the duration of ejection. Neurotransmitter stimulation may provide a more naturalistic means of controlling RGC firing activity for a retinal prosthesis.

Keywords: ganglion cells • excitatory neurotransmitters • retinal degenerations: cell biology 

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