Optogenetic tools and their applications for therapeutic intervention in end-stage inherited retinal diseases

Abstract

Retinal degenerative diseases pose significant therapeutic challenges; however, optogenetic vision restoration offers a promising strategy that is independent of mutations and disease progression. Optogenetic tools consisting of photosensitive membrane proteins can be ectopically expressed in retinal cells, effectively converting them into artificial photoreceptors. This review outlines the development and application of optogenetic tools to restore light sensitivity in degenerated retinas. A thorough understanding of retinal cell morphology, pathological remodeling, and functional loss is critical to identifying optimal cellular targets to maximize retinal signal restoration and achieve challenging visual outcomes. Precise delivery and expression of tailored optogenetic tools in specific retinal cell types is critical for clinical success. While recent efforts have focused on achieving vision restoration at ambient light levels, other considerations such as dynamic light adaptation, inner retinal signal processing, and improved visual resolution have emerged as critical factors. Technologies such as optogenetic stimulation goggles integrated with artificial intelligence have the potential to improve visual quality in treated patients. This review also summarizes the preclinical fundamentals and highlights the first clinical successes, underscoring that optogenetic vision restoration is on its way to becoming an effective therapy for restoring meaningful vision to people affected by blindness.