ВИРУСНЫЕ ВЕКТОРЫ ДЛЯ ОПТОГЕНЕТИЧЕСКОГО ПРОТЕЗИРОВАНИЯ СЕТЧАТКИ

Abstract

For hereditary degenerative diseases of the retina, there are no approaches developed to date that would allow the complete restoration of vision loss after the completion of the active phase of degeneration process. Optogenetic prosthetics of the retina is a promising therapeutic technique, which allows returning the photosensitivity after the death of photoreceptors. It is based on the idea of transforming the surviving retinal neurons expressing photosensitive proteins into pseudo-photoreceptors, and restoring visual function due to central nervous system adaptation to a new signal transduction pathway. The most effective way to deliver genes of photosensitive proteins into the cells of the degenerated retina is to use vectors based on an adeno-associated virus. However, the currently existing vectors do not completely solve the problem of vision restoration, faced with a number of difficulties, and their improvement still continues. Delivery of genetic material to specific types of retinal neurons theoretically can be performed by use of selective promoters that activate gene transcription only in certain cells. But in practice, already developed promoters do not always provide selective gene transduction. Despite the existence of a large number of different photosensitive proteins, including artificially synthesized ones with improved properties, there is no one among them that could by itself provide restored vision with high sensitivity and complex system of signal ON-OFF pathways. The process of viral particles delivery to the retina is also not sufficiently optimized, and problems such as the low capacity of the adeno-associated virus and difficulties in its penetrating through natural barriers of the eye seriously reduce the efficiency of vectors. Successful development of a viral vector suitable for optogenetic prosthetics requires more detailed knowledge of the processes that occur during retinal degeneration, especially at the molecular level.