Optogenetic stimulation of inner retinal neurons restores retinal computations in a virtual degenerated human retina.

Recent advances in genetic engineering have enabled the creation of diverse novel opsins with significant potential for restoring vision. In this study, we introduce a computational model that simulates the human retina's response to optogenetic stimulation across various inner retinal cell types. Our model captures detailed retinal connectivity across multiple neural layers, incorporates conductance-based dynamics at both cellular and synaptic levels, and employs analytical formulations to represent optogenetic processes. Our findings suggest that it is possible to selectively modulate distinct retinal pathways through optogenetic stimulation-even when all photoreceptors are absent-thus potentially reducing off-target effects in clinical trials. Notably, we report two major discoveries: (1) Opsin-expressing AII amacrine cells can replicate the inner retinal signaling observed in healthy retinas, and (2) Opsin-expressing rod bipolar cells demonstrate superior performance compared to other bipolar cell subtypes, likely due to the unique network architecture of the human inner retina.Clinical Relevance- Our work seeks to provide theoretical guidance for future clinical trials while exploring the potential of optogenetics in developing more effective artificial vision therapies.