Abstract
Abstract: :
Purpose: Optimizing the design of electrode arrays for functional stimulation of the retina will require evaluation in an appropriate animal model of retinal degenerative eye disease. The P23H transgenic rat is a proposed model of autosomal dominant retinitis pigmentosa. Here we demonstrate single ganglion cell (GC) responses to electrical stimulation delivered to the photoreceptor side of the retina via an acutely implanted microelectrode array recorded in vivo in a pigmented P23H rat. Methods: Pigmented rats, either wild type (WT, Long Evans) or heterozygous for the P23H transgene (Sprague–Dawley – Long Evans cross) were anesthetized, and a flexible polyimide–based electrode array was surgically positioned between the retina and RPE through a small slit in the sclera. Electrodes remained connected to external stimulus sources via a thin trans–scleral ribbon. A tungsten recording microelectrode was introduced through a needle which pierced the sclera near the limbus, and was advanced to the retinal surface using a robotic micromanipulator. The vitreal electroretinogram and single–cell GC responses to light flash stimuli were routinely recorded with the tungsten microelectrode. Monophasic and biphasic square pulse constant current stimuli were delivered through paired (active / reference) subretinal electrodes (bare gold or gold coated with platinum black) ranging in size from 20 – 500 µm diameter.Results: Spike trains from single ganglion cells were recorded in response to light and in response to subretinal electrical stimulation (WT and P23H rats). The recording electrode could be scanned across the retinal surface to determine the local population of GCs responding to a given electrode pair.Conclusions:An experimental approach has been developed to allow experimental evaluation of various electrode configurations and stimulus waveforms in an animal model of retinal degenerative disease. Measurements are made in vivo. Electrode arrays of arbitrary design, motivated by experimental results and complimentary computational models, can be fabricated in a few days.
Keywords: electroretinography: non–clinical • ganglion cells • receptive fields