Optimal Electric Stimulus Amplitude Improves the Selectivity Between Responses of ON Versus OFF Types of Retinal Ganglion Cells

Abstract

Outer retinal degenerative diseases destroy photoreceptors primarily in the retina, resulting in a profound vision loss. Fortunately, surviving retinal neurons can be electrically stimulated using retinal prostheses to re-transmit visual information. Although retinal prostheses are promising for sight restoration, the best performance is still sub-optimal. For the enhanced performance, it is critical to optimize stimulation parameters. This study explored how stimulus charge and current amplitude alters responses of retinal ganglion cells (RGCs). From the isolated mouse retina, spiking activities of alpha ON, OFF sustained, and OFF transient RGCs were recorded in response to epiretinally-delivered cathodal current pulses ranging from -10 to -80 mu A. We have found that intermediate current amplitudes (-30 and -40 mu A) maximize the response ratio of ON over OFF types. Also, the ON/OFF response ratio was always bigger for 10-ms-long than 5-ms-long stimuli. It was because, by the longer pulses, ON RGC responses were always significantly enhanced (p < 0.05) while OFF RGC responses were minimally changed (p > 0.05). Given the earlier work reporting electrically-elicited responses are more natural in ON than OFF RGCs, the present study suggests effect strategies of more selective activation of ON RGCs for improved efficacy of retinal implant.