Chemical stimulation of XXXX retinal neurons: feasibility of an epiretinal neurotransmitter-based prosthesis.

@entity1 @entity2227 @entity1939 @entity179 @entity35
UNASSIGNED: Objective. No cure currently exists for @entity179 , which cause @entity1939 in millions of @entity1 worldwide. Electrical retinal prostheses have been developed by several groups with the goal of restoring vision lost to these diseases, but electrical stimulation has limitations. It excites both somas and axons, activating retinal pathways nonphysiologically, and limits spatial resolution because of current spread. Chemical stimulation of retinal ganglion cells (RGCs) using the neurotransmitter @entity2227 has been suggested as an alternative to electrical stimulation with some significant advantages. However, sufficient scientific data to support developing a chemical-based retinal prosthesis is lacking. The goal of this study was to investigate the feasibility of a neurotransmitter-based retinal prosthesis and determine therapeutic stimulation parameters. Approach. We injected controlled amounts of @entity2227 into @entity35 retinas from the epiretinal side ex vivo via micropipettes using a pressure injection system and recorded RGC responses with a multielectrode array. Responsive units were identified using a spike rate threshold of 3 Hz. Main results. We recorded both somal and axonal units and demonstrated successful glutamatergic stimulation across different RGC subtypes. Analyses show that exogenous @entity2227 acts on RGC synapses similar to endogenous @entity2227 and, unlike electrical prostheses, stimulates only RGC somata. The spatial spread of @entity2227 stimulation was [Formula: see text]  m from the injection site, comparable to current electrical prostheses. Further, the @entity2227 injections produced spatially differential responses in OFF, ON, and ON-OFF RGC subtypes, suggesting that differential stimulation of the OFF and ON systems may be possible. A temporal resolution of 3.2 Hz was obtained, which is a rate suitable for spatial vision. Significance. We provide strong support for the feasibility of an epiretinal neurotransmitter-based retinal prosthesis. Our findings suggest that chemical stimulation of RGCs is a viable alternative to electrical stimulation and could offer distinct advantages such as the selective stimulation of RGC somata.
