Abstract

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.

Highlights

  • Retinal degenerative diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), are major causes of blindness in ­adults[1,2]

  • We focused on the responses of individual retinal ganglion cell (RGC) using an in-vitro multi-electrode array (MEA) recording setup to identify changes in light responsiveness in local areas (2 mm × 2 mm) of the retinal tissue, not the whole retina (Fig. 1A)

  • If the tested retinal patch did not respond to light stimulus (LS), we classified the retinal patch as a severe retinal degeneration (RD) group

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Summary

Introduction

Retinal degenerative diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), are major causes of blindness in ­adults[1,2]. Epiretinal stimulation exhibits better efficacy when cathodic phasefirst biphasic pulses are used, whereas subretinal stimulation exhibits better efficacy in case of anodic phase-first biphasic ­pulses[22,23] As these studies examined only lower mammals, such as mice, rats, and rabbits, it is difficult to extrapolate their results to patients with RD. Sekirnjack et al reported no remarkable differences in RGC responses among monkeys, guinea pigs, and rats under the same stimulation ­conditions[19], further research is required in this regard. Because their results were analyzed based only on the direct RGC responses with a short latency (less than 20 ms) without considering indirect responses of RGCs, investigating the indirect responses of RGCs through retinal synapses among different mammals is crucial

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