Progressive Retinal Degeneration Increases Cortical Response Latency of Light Stimulation but Not of Electric Stimulation

Abstract

Purpose The brain is known to change functionally and structurally in response to blindness, but less is known about the effects of restoration of cortical input on brain function. Here, we present a preliminary study to observe alterations in visual and electrical evoked cortical potentials as a function of age in a clinically relevant animal model of retinitis pigmentosa. Methods We recorded brain potentials elicited by light (visual evoked potentials [VEPs]) or corneal electrical stimulation (electrical evoked response [EER]) in retinal degenerate animal model LE-P23H-1. We used a linear mixed model to examine the effects of age on latency and amplitude of VEP and EER age groups P120, P180, and P360. Results VEP N1, P1, and N2 latency and amplitude were analyzed across animal age. For 1 Hz VEP, N1 latency increased significantly with animal age (slope = 0.053 ± 0.020 ms/day, P < 0.01). For 10 Hz VEP, N1, P1, and N2 latency increased significantly with animal age (slope = 0.104 ± 0.011, 0.135 ± 0.011, 0.087 ± 0.023 ms/day, and P < 0.001 for all VEP peaks). Conversely, EER latency did not change with age. Signal amplitude of VEP or EER did not change with age. Conclusions Cortical potentials evoked by electrical stimulation of the retina do not diminish in spite of continued retinal degeneration in P23H rats. Translational Relevance These findings suggest that retinal bioelectronic treatments of retinitis pigmentosa will activate cortex consistently despite variations in outer retinal degeneration. Clinical studies of retinal stimulation should consider varying retinitis pigmentosa genotypes as part of the experimental design.

Pre- and postsynaptic alterations in the visual cortex of the P23H-1 retinal degeneration rat model

“…However, such changes have not yet been described. In any case, the pathways that connect ganglion cells to visual cortex are relatively preserved because cortical potentials evoked by electrical stimulation of the retina in P23H rats do not decrease compared to the control rats ( Koo and Weiland, 2022 ). In other model of photoreceptor degeneration, the rd10 mouse, the decrease in cortical activities upon visual stimulation also correlates with retinal degeneration progression ( Narcisse et al, 2021 ).…”