Electrical response of retinal ganglion cells in an N-methyl-N-nitrosourea-induced retinal degeneration porcine model

Retinal prosthesis is regarded as the treatment for vision restoration in the blind with retinal degeneration (RD) due to the loss of photoreceptors. A strategy for retinal prosthesis is to electrically activate surviving neurons. The retina’s response to electrical stimulation in a larger RD model has not been studied yet. Therefore, in this study, we investigated electrically evoked retinal responses in a previously validated N-methyl-N-nitrosourea (MNU)-induced porcine RD model. Electrically evoked responses were evaluated based on the number of retinal ganglion cell (RGC) spikes via multichannel recordings. Stimulation pulses were applied to degenerative and wild-type retinas with pulse modulation. Compared to wild-type retinas, degenerative retinas showed higher threshold values of pulse amplitude and pulse duration. The rate of increase in the number of RGC spikes relative to stimulus intensity was lower in degenerative retinas than in normal retinas. In severely degenerated retinas, few RGCs showed electrically evoked spikes. Our results suggest that the degenerative porcine retina requires a higher charge than the normal porcine retina. In the early stage of RD, it is easier to induce RGC spikes through electrical stimulation using retinal prosthesis; however, when the degeneration is severe, there may be difficulty recovering patient vision.

Choroideremia

Choroideremia is X-linked chorioretinal dystrophy characterized by progressive degeneration of the choroid, retinal pigment epithelium (RPE), and retina. The disease is caused by mutations in the CHM gene which is known to be related to membrane transportation protein in the retina and RPE. Male-affected cases have nyctalopia and progressive reduction in visual acuity. Female-affected cases are carriers. This disease is considered incurable, although new promising treatments have been recently introduced such as gene therapy, stem cells, small molecules, and retinal prosthesis.

A Computational Model of Phosphene Appearance for Epiretinal Prostheses

Retinal neuroprostheses are the only FDA-approved treatment option for blinding degenerative diseases. A major outstanding challenge is to develop a computational model that can accurately predict the elicited visual percepts (phosphenes) across a wide range of electrical stimuli. Here we present a phenomenological model that predicts phosphene appearance as a function of stimulus amplitude, frequency, and pulse duration. The model uses a simulated map of nerve fiber bundles in the retina to produce phosphenes with accurate brightness, size, orientation, and elongation. We validate the model on psychophysical data from two independent studies, showing that it generalizes well to new data, even with different stimuli and on different electrodes. Whereas previous models focused on either spatial or temporal aspects of the elicited phosphenes in isolation, we describe a more comprehensive approach that is able to account for many reported visual effects. The model is designed to be flexible and extensible, and can be fit to data from a specific user. Overall this work is an important first step towards predicting visual outcomes in retinal prosthesis users across a wide range of stimuli.