Cortical responses to prosthetic retinal stimulation are significantly affected by the light-adaptive state of the surrounding normal retina

Abstract

Objective. Restoration of central vision loss in patients with age-related macular degeneration (AMD) by implanting a retinal prosthesis is associated with an intriguing situation wherein the central prosthetic vision co-exists with natural normal vision. Of major interest are the interactions between the prosthetic and natural vision. Here we studied the effect of the light-adaptive state of the normal retina on the electrical visual evoked potentials (VEPs) arising from the retinal prosthesis. Approach. We recorded electrical VEP elicited by prosthetic retinal stimulation in wild-type rats implanted with a 1 mm photovoltaic subretinal array. Cortical responses were recorded following overnight dark adaption and compared to those recorded following bleaching of the retina by light (520 nm) at various intensities and durations. Main results. Compared to dark-adapted responses, bleaching induced a 2-fold decrease in the prosthetic cortical response, which returned to the dark-adapted baseline within 30 min to several hours, depending on the degree of bleaching. This reduction was neither observed in Royal College of Surgeons (RCS) rats with a degenerated photoreceptor layer nor following intravitreal injection of a GABAa receptor blocker (bicuculine), suggesting the involvement of photoreceptors and a GABAa-mediated mechanism. Significance. These findings show a robust effect of the retinal light-adaptive state on the obtained prosthetic responses. If a similar effect is found in humans, this will have immediate implications on the design of prosthetic devices, where both natural and prosthetic vision co-exist, such as in AMD patients receiving a photovoltaic retinal implant. Similarly, standardization of the retinal light-adaptive state in prosthetic clinical trials should be considered.

Expression of Channelrhodopsin‐2 in Rod Bipolar Cells Restores ON and OFF Responses at High Spatial Resolution in Blind Mouse Retina

“…[68] However, Barone et al [28] reported a positive visual behavior for 1-year-old rd10 mice. Residual vision, which may originate from ectopic synapses between cones and rBCs, [69] needs to be considered when evaluating artificial vision, [70] since the inner retina relays information between the naturally activated retinal circuitry and prosthetic percepts. Long-range information transmission in the retina, [71] together with non-homogeneous optogenetic transduction achieved in humans, may lead to a complex visual percept.…”

A novel GCaMP6f-RCS rat model for studying electrical stimulation in the degenerated retina

“…Focal electroretinogram (fERG) recordings were performed using the Micron IV (Phoenix Research Laboratories, Inc.) equipped with a focal ERG stimuli module; the electrophysiological response was recorded using the AlphaSNR recording system (Alpha Omega Ltd., Israel), similar to our previous publications ( Arens-Arad et al, 2020 ; Arens-Arad et al, 2021 ). Animals were anesthetized and the pupils were dilated with Mydramide (0.5% Tropicamide, Fisher Pharmaceuticals, Ltd.) and Efrin-10 (10% Phenylephrine HCL, Fisher Pharmaceuticals Ltd.) drops.…”