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R. Iezzi, N.P. Cottaris, S.D. Elfar, T.L. Walraven, T.M. Raza, R. Moncrieff, J.P. McAllister, G.W. Auner, R.R. Johnson, G.W. Abrams; Neurotransmitter-Based Retinal Prosthesis Modulation of Retinal Ganglion Cell Responses In-Vivo . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5083.
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Purpose:The tissue interface component of a retinal prosthesis must communicate visual information from a camera or set of detectors to retinal neurons. Signaling within the retina occurs predominantly through neurotransmitter synapses between cells. While electrical stimulation has proven efficacy in eliciting electrophosphene percepts in humans, the resolution and variety of visual percepts has been limited. The purpose of this study is to determine the efficacy with which a neurotransmitter-based retinal prosthesis can modulate retinal ganglion cell responses, in-vivo. Methods: Adult cats were anesthetized using sevofluorane, and paralyzed with pancuronium bromide. Retinal ganglion cell (RGC) responses were recorded using hybrid extracellular carbon fiber electrodes, coupled to 3 micron diameter microfluidic channels. A specially designed trochar system permitted insertion of the device into the eye without tip damage. Post-stimulus time histograms (PSTHs) were Fourier analyzed to measure the effects of neurotransmitter on response. Acetylcholine and other neurotransmitters were iontophoretically delivered to the epiretinal surface within 1 micron of the carbon fiber. Results: RGC responses were characterized during light on and off transitions. We observed two major influences of acetylcholine in decrement-excitatory RGCs. The application of acetylcholine reduced inhibition during the increment excitatory-response. In addition, Fourier analysis of the PSTHs demonstrated that acetylcholine induced a shift in the cells' intrinsic firing frequency from a 37 Hz broadly tuned response to a narrowly tuned 45 Hz oscillation. Conclusions: Overall, our work demonstrates the feasibility of delivering neurotransmitters to the epiretinal surface in a spatially and temporally controlled manner while simultaneously recording RGC responses, in-vivo. The design of retinal prostheses that generate more complex percepts than electrophosphenes will require a database that documents the efficacy of different neurotransmitters on various RGC types.
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