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Corey Michael Rountree, Samsoon Inayat, John B Troy, Laxman Saggere; Feasibility of a biomimetic neurotransmitter-based retinal prosthesis: Subretinal glutamate injections produce differential responses in OFF and ON pathways of rat retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3240.
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© ARVO (1962-2015); The Authors (2016-present)
Electrical stimulation of photoreceptor degenerated retinas can restore rudimentary vision in patients, but has difficulty achieving high spatial resolutions or differential stimulation of the OFF and ON pathways. To address these shortcomings, we explored the use of the neurotransmitter glutamate to chemically stimulate outer retinal neurons to determine the feasibility of a subretinal microfluidics-based retinal prosthesis.
Whole retinas from wild-type Long-Evans rats (N=16) were explanted and placed retinal ganglion cell (RGC) side down on multielectrode arrays to obtain spike data from RGCs and local field potentials (LFPs) from other retinal neurons. An LCD display was used to visually stimulate retinas with Gaussian white-noise checkerboards to identify the receptive field locations and, through the use of non-centered spike triggered non-covariance analyses, the types of recorded RGCs. Data analyses and spike sorting were performed with custom Matlab code. Glutamate (1mM) was injected ∼70 μm within the subretinal surface near the outer plexiform layer using a micropipette, pressure injector (0.1PSI), and micromanipulator.
Subretinal glutamate injections generated responses in ON (N=46), OFF (N=90), and ON-OFF (N=303) RGCs. A total of 132 sets of glutamate injections produced coincident and colocalized responses in OFF and ON RGCs, 85 (64%) of which elicited differential responses by inhibiting OFF RGCs and exciting ON RGCs (Fig. 1). Examination of the LFP responses to glutamate injections revealed slow-wave activity consistent with stimulation of outer retinal neurons. Responsive units were localized near the site of injection with a median spread of 210 μm (lower, upper quartiles: 96, 400 μm).
Our results indicate that a subretinal neurotransmitter-based retinal prosthesis is feasible and can produce differential responses in the OFF and ON pathways in wild-type rats with high spatial resolution. Further experiments with a photoreceptor degenerated model are needed to conclusively demonstrate the feasibility of a neurotransmitter-based retinal prosthesis.
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