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Ralph J. Jensen, Joseph F. Rizzo, III; Electrical Stimulation Of Retinal Ganglion Cells In Degenerate Rat Retina With A Small Subretinal Electrode. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5542.
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© ARVO (1962-2015); The Authors (2016-present)
Previously we investigated the thresholds for activation of retinal ganglion cells (RGCs) in the degenerate (P23H) rat retina with a large (400-µm diameter) subretinal electrode. Recent clinical trials are now utilizing smaller (50-200 µm) electrodes. The purpose of this study was to investigate the responses of P23H rat RGCs to subretinal stimulation with a 125-µm electrode.
Extracellular recordings were made from P23H rat RGCs in the isolated retina. Biphasic current pulses (1 ms per phase) were delivered to the subretinal surface through a 125-µm diameter electrode. Thresholds for eliciting electrically evoked responses were determined for RGCs that were directly above the stimulating electrode and at known distances from the stimulating electrode. For comparison with the results obtained in P23H rats, similar experiments were conducted in Sprague-Dawley (SD) rats.
We investigated the electrically evoked spike activity from RGCs that arose from stimulation of the retinal neural network. Thresholds for activation of 25 SD rat RGCs and 16 P23H rat RGCs were obtained with the recording electrode placed over the stimulating electrode. Thresholds of SD rat RGCs ranged from 0.52 to 2.8 µA; thresholds of P23H rat RGCs ranged from 1.2 to 7.8 µA. Median thresholds of RGCs were 1.4 µA in SD rats and 2.5 µA in P23H rats. We examined how thresholds of RGCs change as a function of distance (100-500 µm) from the center of the stimulating electrode. Threshold data were collected from 61 SD rat RGCs and 78 P23H rat RGCs. The median threshold currents of RGCs were much higher in P23H rat for all distances. What was striking was that the thresholds for activation of RGCs in P23H rat retinas rose much more rapidly. When the recording electrode was only 100-200 µm from the center of the stimulating electrode, the median threshold of P23H rat RGCs rose by 460%. In contrast, the median threshold current of SD rat RGCs increased only 29%.
We found that the thresholds for indirect stimulation of both SD and P23H rat RGCs with a 125-µm diameter electrode are much lower than what we found previously with a 400 µm-diameter electrode. The median threshold current was 4.3-fold lower for SD rat RGCs and 7.2-fold lower for P23H rat RGCs. To achieve high resolution vision, the spread of activation of RGCs needs to be limited. Our findings indicate that the spread of activation of RGCs is more confined in the degenerate retina.
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