Optogenetics for therapeutic use in the brain, eye, and ear

Optogenetics is the process of photosensitizing cells and thereby controlling their activity with light. The discovery of channelrhodopsins has allowed for a reversible, spatiotemporally precise method to activate or silence specific target cells, unlike any previous methodologies. As such, this tool has revolutionized the way we study and deconstruct neural circuits, allowing us to begin to clarify some of the cellular mechanisms behind many neurologic conditions such as Parkinson disease and epilepsy. As these are, in principle, neuromodulatory tools, they have been envisioned as potential treatments that can target and reverse pathologic pathways in the brain. Thus, in the recent years, there is a great interest in therapeutic optogenetics, centered mainly around restoration of the major senses of vision and hearing. This chapter will first highlight the ongoing evolution of optogenetics from an investigative tool to a therapeutic one, illustrated by few examples of the most promising areas where optogenetics shine. As the eye is at the forefront of gene therapy, this chapter will particularly focus on optogenetics being gene agnostic approach to restore vision in the late-stage retinal degenerations, with discussion of the importance of opsin and cellular selection and a summary of the current clinical trials in this field thus far.