Optogenetics and prosthetic treatment of retinal degeneration

Abstract

This is a review of the current state of optogenetics-based research in the field of ophthalmology and physiology of vision. Optogenetics employs an interdisciplinary approach that amalgamates gene engineering, optics, and physiology. It involves exogenous expression of a light-activated protein in a very particular retinal cell enabling regulation (stimulation vs. inhibition) of its physiological activity. The experience with gene therapy came in very useful for optogenetics. However, unlike gene therapy, which is aimed at repairing damaged genes or replacing them with healthy ones, optogenetics is focused on protein genes delivery for further molecular control of the cell. In retina, the loss of photoreceptors is not necessarily followed by neuronal loss (at least ganglion cells remain intact), which determines the practicability of prosthetic treatment. Clinical trials can now be considered, owing to the first successful conversion of ganglion cells of mouse degenerative retinas into artificial photoreceptive cells with ON and OFF receptive fields, which is crucial for spatial vision. The following issues are reviewed here in detail: 1. Choice of cell targets within the degenerative retina. 2. Strategy of utilizing the existing light-sensitive agents and development of new optogenetic tools. 3. Gene delivery and expression in retinal cells. 4. Methods of evaluating the treatment success. 5. Selection criteria for optogenetic prosthetics. The conclusion discusses currently unsolved problems and prospects for optogenetic approaches to retinal prosthetics.

The first deaf-blind patient in Russia with Argus II retinal prosthesis system: what he sees and why

“…They are difficult in terms of surgery access owing to the deep location of the functional cortex, and also because they have not attracted much interest from researchers, while cortical implants are fixed on the surface of the visual cortex of the brain, are easily accessed during surgery and are being actively developed by a number of research groups. Optogenetic therapy is based on a transformation of retinal neurons (ganglion cells, bipolar cells and the inner segment of photoreceptors) to photosensitive cells through implanting into their membrane photosensitive proteins [15]. This technology appears to be quite promising because it allows us to obtain a high density and clearer visual signal from the retina as specific cells are activated, while the electrical signal from the electrodes activate many neurons of different types in several layers simultaneously, which spoils the signal to the visual cortex.…”