Virus Vectors for Optogenetic Prosthetization of the Retina

Abstract

No approaches completely restoring lost vision after completion of the active phase of degeneration have as yet been developed for inherited degenerative diseases of the retina. Optogenetic prosthetization of the retina is a potential therapeutic method returning light sensitivity after the death of photoreceptors. This is based on the idea that surviving retinal neurons can be converted into pseudophotoreceptors by expressing light-sensitive proteins within them and restoring visual function via adaptation of the central nervous system to the new signal transmission pathway. The most effective way to deliver genes for light-sensitive proteins into cells in the degenerative retina consists of using vectors based on adeno-associated virus. However, current vectors do not completely solve the task of restoring vision and they continue to be improved. Delivery of genetic material to specific types of retinal neurons is theoretically possible using selective promoters activating the transcription of a gene only in defined cells. However, in practice, promoters which have already been developed do not always provide selective gene transduction. Despite the existence of many different light-sensitive proteins, including artificially synthesized proteins with improved properties, there are none which alone support restoration of vision with high sensitivity and a complex ON/OFF signal pathway system. The process of delivery of virus particles to the retina is also not sufficiently optimized, and problems such as the small capacity of adeno-associated virus and difficulties in its penetration across natural barriers seriously decrease the effectiveness of vectors. Successful development of a virus vector suitable for optogenetic prosthetization requires more detailed knowledge of the processes occurring in retinal degeneration, particularly at the molecular level.