Opsins and Their Testing in Heterologous Expression Systems

Light-sensitive proteins are potential optogenetic tools for restoring visual functions in degenerated photoreceptors in the retina. A detailed study of their properties in heterologous expression systems is a necessary step preceding animal experiments. The features of opsins and factors influencing their activity in model cell systems are considered. Particular attention is paid to G-protein-coupled opsins as promising tools for recreating the signaling cascade mechanisms of ON-bipolar retinal cells. Light-controlled signaling pathways activated by natural or chimeric opsins, opening G-protein-gated inwardly rectifying potassium channels (GIRKs), as well as possible modulation of intracellular signaling mediated by G proteins, are analyzed. It has been shown that comparison of the characteristics of light stimulation (spectral range, intensity, duration, and frequency) with the obtained photobiological responses of cells (amplitude of channel currents, kinetics of activation and deactivation of channels) in a test heterologous expression system allows selecting the best candidates among light-sensitive proteins that are promising in gene therapy.