Computational framework and tools for evaluating engineered channelrhodopsin performance in a degenerated retina.

Recent breakthroughs in genetic engineering have paved the way for the development of a range of novel opsins with promising applications in visual restoration through optogenetics. We present a computational model that combines analytical formulations of optogenetic mechanisms with conductance-based representations of cellular and synaptic properties. Through systematic optimization, our model now provides a robust framework for simulating and analyzing the functional dynamics of these newly developed opsins. Moreover, by calibrating our model with the latest preclinical data in optogenetics and human retinal physiology, our findings reveal that emerging channelrhodopsins exhibit enhanced stimulation efficiency in human retinal ganglion cells within degenerated retinae.Clinical Relevance-This simulation tool offers valuable insights for advancing experimental and translational research in optogenetic vision restoration, serving as a predictive platform for evaluating novel opsins.