gms | German Medical Science

Objective: To directly characterize the temporal activation of retinal bipolar cells in response to repetitive electrical stimulation.

Introduction: Retinal prostheses electrically stimulate the retina in order to restore vision in patients blinded by retinitis pigmentosa. Electrical stimulation can directly activate retinal ganglion cells, or indirectly activate them through the depolarization of bipolar cells which in turn synaptically activate the downstream ganglion cells. Desensitization to stimulation is observed both clinically and in vitro, but the cause has yet to be determined.

Methods: Retinas from transgenic Tg(Gng13-EGFP)GI206Gsat mice with a C57BL/6J background were isolated in Ames’ media. Photoreceptors were mechanically removed using filter paper. Retinas were mounted ganglion cell-side down on a microelectrode array and stimulated through a 200µm-diameter electrode with 25-ms cathodic-first, controlled-current pulses at frequencies ranging from 1-20Hz. Whole cell current clamp recordings were obtained from the soma of ON-type bipolar cells.

Results: Bipolar cells responded to electrical stimulation with fast spike-like voltage depolarizations. From six cellular recordings, we find that bipolar cells responded consistently to 25-ms pulses delivered at frequencies below 6Hz. However, above 6Hz, the response strength was reduced within seconds of the stimulus onset.

Discussion: The time-decaying response measured in bipolar cells suggests that a mechanism contributing to retinal desensitization originates within bipolar cells and does not involve synaptic vesicle depletion.

Supported by: NEI EY022931, NEI EY022931-S1, The National GEM Consortium, Research to Prevent Blindness, W.M. Keck Foundation, NSF EEC-031072.