Inherited and age-related retinal degenerative diseases cause progressive loss of photoreceptors, ultimately leading to blindness. Optogenetics is a promising strategy for restoring visual function through photosensitive proteins’ ectopic expression in surviving retinal neurons. Very recently, the optogenetic method with a red-shifted Channelrhodopsin was clinically applied for partial recovery of visual function in a blind patient. However, major obstacles to achieving optimal optogenetic vision restoration are either the low light sensitivity or the slow kinetics of existing rhodopsin-based optogenetic tools, which can be improved by molecular engineering to enhance the efficacy of fast Channelrhodopsins (ChRs). Here, we present a newly engineered ChR variant PsCatCh2.0, engineered from PsChR, which displays inherently high Ca2+ and Na+ conductance and fast kinetics.
