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

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.

Cortical Interactions between Prosthetic and Natural Vision.

Outer retinal degenerative diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), are among the leading causes of incurable blindness in the Western world [1]. Retinal prostheses have been shown to restore some useful vision by electrically stimulating the remaining retinal neurons [2]. In contrast to inherited retinal degenerative diseases (e.g., RP), typically leading to a complete loss of the visual field, in AMD patients the disease is localized to the macula, leaving the peripheral vision intact. Implanting a retinal prosthesis in the central macula in AMD patients [3, 4] leads to an intriguing situation where the patient's central retina is stimulated electrically, whereas the peripheral healthy retina responds to natural light stimulation. An important question is whether the visual cortex responds to these two concurrent stimuli similarly to the interaction between two adjacent natural light stimuli projected onto healthy retina. Here, we investigated the cortical interactions between prosthetic and natural vision based on visually evoked potentials (VEPs) recorded in rats implanted with photovoltaic subretinal implants. Using this model, where prosthetic and natural vision information are combined in the visual cortex, we observed striking similarities in the interactions of natural and prosthetic vision, including similar effect of background illumination, linear summation of non-patterned stimuli, and lateral inhibition with spatial patterns [5], which increased with target contrast. These results support the idea of combined prosthetic and natural vision in restoration of sight for AMD patients.

Head mounted DMD based projection system for natural and prosthetic visual stimulation in freely moving rats.

Novel technologies are constantly under development for vision restoration in blind patients. Many of these emerging technologies are based on the projection of high intensity light patterns at specific wavelengths, raising the need for the development of specialized projection systems. Here we present and characterize a novel projection system that meets the requirements for artificial retinal stimulation in rats and enables the recording of cortical responses. The system is based on a customized miniature Digital Mirror Device (DMD) for pattern projection, in both visible (525 nm) and NIR (915 nm) wavelengths, and a lens periscope for relaying the pattern directly onto the animal's retina. Thorough system characterization and the investigation of the effect of various parameters on obtained image quality were performed using ZEMAX. Simulation results revealed that images with an MTF higher than 0.8 were obtained with little effect of the vertex distance. Increased image quality was obtained at an optimal pupil diameter and smaller field of view. Visual cortex activity data was recorded simultaneously with pattern projection, further highlighting the importance of the system for prosthetic vision studies. This novel head mounted projection system may prove to be a vital tool in studying natural and artificial vision in behaving animals.