0257 GMT January 20, 2020
However, several factors limit the feasibility of a clinical optogenetic therapy using traditional light-sensitive proteins, as they require unnaturally high and potentially harmful light intensities and employ a foreign signaling mechanism within the target retinal cells, Medical Xpress reported.
The novel light-sensing protein, termed Opto-mGluR6, is a chimeric protein composed of the light-sensing domains of the retinal photopigment melanopsin and the ON-bipolar cell-specific metabotropic glutamate receptor mGluR6, which is naturally activated by glutamate released from the photoreceptors and amplifies the incoming signal through a coupled intracellular enzymatic pathway.
Unlike rhodopsin, for example, the "light antenna" of melanopsin is resistant to bleaching. In other words, the response strength of Opto-mGluR6 never attenuates, no matter how often and hard the protein is hit by light. Moreover, since Opto-mGluR6 is a chimeric protein consisting of two "local" retinal proteins, it is also likely to be "invisible" to the immune system, another improvement over traditional optogenetic proteins.
In their study, researchers targeted the retinal ON-bipolar cells, which naturally receive direct input from the photoreceptors.
Targeting the surviving cells at the top end of the visual cascade has the advantage that signal computation of the retina is maximally utilized. Turning the native chemical receptor (mGluR6) into a light-activated receptor ensures conservation of native signaling within the ON-bipolar cells, conferring high light-sensitivity and fast "normal" responsiveness. In their study, they show proof-of-principle that mice suffering from Retinitis pigmentosa can be treated to regain daylight vision. "The new therapy can potentially restore sight in patients suffering from any kind of photoreceptor degeneration" said Dr. Sonja Kleinlogel, corresponding author of the paper from the University of Berne, Switzerland, "for example also those suffering from severe forms of age-related macular degeneration, a very common disease that affects to some degree about one in every 10 people over the age of 65".