Optogenetic Approaches to Restoring Vision.

Severe loss of photoreceptor cells in inherited or acquired retinal degenerative diseases can result in partial loss of sight or complete blindness. The optogenetic strategy for restoration of vision utilizes optogenetic tools to convert surviving inner retinal neurons into photosensitive cells; thus, light sensitivity is imparted to the retina after the death of photoreceptor cells. Proof-of-concept studies, especially those using microbial rhodopsins, have demonstrated restoration of light responses in surviving retinal neurons and visually guided behaviors in animal models. Significant progress has also been made in improving microbial rhodopsin-based optogenetic tools, developing virus-mediated gene delivery, and targeting specific retinal neurons and subcellular compartments of retinal ganglion cells. In this article, we review the current status of the field and outline further directions and challenges to the advancement of this strategy toward clinical application and improvement in the outcomes of restored vision.