Modulation Of Retinal Response To Photovoltaic Stimulation By Pulse Duration And Irradiance

Abstract

Purpose: : To restore sight to patients blinded by degenerative retinal diseases using photovoltaic stimulation of the surviving inner retinal neurons. Visual information is delivered by projecting images onto a subretinal silicon photodiode array using pulses of near-infrared (880nm) light, which are converted into bi-phasic pulses of electric current in each pixel. We evaluate retinal response to such stimulation using a multielectrode recording array.

Methods: : An isolated retina was placed ganglion cell (RGC) side down on a high-density transparent multielectrode array. Two types of silicon photodiode arrays were tested. They were both placed on the photoreceptor side of the retina and illuminated with 880nm light. One implant has pixels consisting of a single diode with global return. In the 2nd generation device each pixel has 3 diodes and a local return electrode to increase dynamic range and facilitate local stimulation. Experiments were done with wild type (WT, Long-Evans) and degenerate (RCS) rat retina. Visual responses of WT RGCs were also characterized using a spatio-temporal white noise stimulus projected onto the photoreceptor layer.

Results: : RGC spikes were reproducibly elicited in healthy and degenerate retina by IR stimulation with pulse durations in the range 0.5 - 4 ms. Spike trains with latencies up to 80 ms were observed. Single diode and 3-diode devices exhibited similar full-field threshold peak irradiance of ~0.3 mW/mm² for WT retina and ~0.8 mW/mm² for RCS retina (4ms pulses). Local response to single-pixel stimulation was achieved on 3-diode pixels with 40μm diameter active electrodes at the threshold of ~5 mW/mm² (4ms pulses). The measured thresholds were 2 orders of magnitude below the ocular safety limit.The average number of spikes elicited by an IR pulse varied from 0.5 at the stimulation threshold to about 4 with increased stimulus irradiance and/or pulse duration. The frequency of the spikes in an elicited burst reached as high as 100 Hz.

Conclusions: : We demonstrate that it is possible to safely and reproducibly elicit RGC spiking mediated by stimulation of the inner retinal neurons using a photovoltaic subretinal implant illuminated with pulsed IR light. Retinal response to stimulation can be modulated by both brightness and duration of the IR pulse, and spatial localization is possible with pixels having local return electrodes.

Keywords: retina • electrophysiology: non-clinical • ganglion cells