Probing the Impact of Inner Retinal Network Changes on Subretinal Electrical Stimulation Responses.

We investigated the influence of degenerated retinal networks on the efficacy of subretinal prosthetic devices in eliciting retinal neural responses. We present a computational model that incorporates intricate descriptions of retinal connectivity spanning neural layers, conductance-based cellular and synaptic parameters, and analytical formulas governing the electrical field. Our results suggest the possibility of selective modulation of functionally-distinct retinal pathways through subretinal stimulation, even in the absence of all photoreceptors. However, we observed a decreasing level of selectivity as inter-neuron synapse and gap junctions were progressively reduced. In addition, our model predicts a more pronounced influence of the integrity of the inner retinal network on electrically induced OFF compared to ON retinal ganglion cell activity. This phenomenon is ascribed to the unique inner retinal network properties of ON versus OFF pathways and changes in these properties upon photoreceptor loss. By precisely controlling the parametric values defining synaptic and gap junction connectivity in the inner retina, we can simulate the impact of different degrees of retinal degeneration on the retina's response to electrical stimulation. This model can assess the retinal network's response to remodeling events across different retinal degeneration stages, offering insights to guide the future development of retinal prosthetic devices and stimulation strategies. Such advancements hold promise for benefiting patients at various stages of retinal disease progression.