Retinal Response To Photovoltaic Stimulation In Normal And Degenerated Retinas

Abstract

Purpose: : Electronic retinal prostheses seek to restore sight to blind patients with degenerative retinal diseases by delivering patterned electrical stimulation to surviving retinal neurons. One approach is to deliver visual information by projecting images onto a subretinal silicon photodiode array using pulses of near-infrared (IR) light, which is then converted into bi-phasic pulses of electric current in each pixel. We evaluated this approach in-vitro.

Methods: : An isolated retina was placed ganglion cell (RGC) side down on a high-density transparent multielectrode array (512 electrodes spaced at 60 µm). The silicon photodiode array was placed on the other side of the retina and illuminated with IR light (880 nm). Synaptic blockers were used to ascertain which retinal neuronal types were stimulated. Experiments were done with wild type (Long-Evans LE) and degenerated (RCS) rat retina. Visual responses of LE RGCs were characterized using a spatio-temporal white noise stimulus projected onto the photoreceptor layer.

Results: : RGC spikes were reproducibly elicited in healthy (LE rat) retina by IR stimulation with pulse durations in the range 0.1-4 ms. Individual spikes with shorter latencies (~3 ms) and spike trains with longer latencies (up to 50 ms) were observed. The stimulation threshold was measured to be around 1 mW/mm2 peak irradiance, corresponding to 1.6 µW/mm2 average irradiance (for 2 Hz pulse frequency). L-AP4 (an mGluR6 receptor agonist) blocked visual responses of ON RGCs, but did not affect their responses to photovoltaic stimulation indicating that the photoreceptor layer is not activated by the stimulation pulses. DNQX (a non-NMDA antagonist) and DL-AP7 (an NMDA antagonist) suppressed RGC responses to the photovoltaic stimulation indicating that RGC stimulation is mediated by inner-retinal neurons. The stimulation thresholds and response latencies of the RCS retina were measured to be similar to those of the LE retina.

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. Importantly, the degenerate retina can be reliably stimulated despite the substantial re-wiring known to occur.

Keywords: retina • visual impairment: neuro-ophthalmological disease • electrophysiology: non-clinical