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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)
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.
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.
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.
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.
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