In vivo optogenetic stimulation of the primate retina activates the visual cortex after long-term transduction

Over the last 15 years, optogenetics has changed fundamental research in neuroscience and is now reaching toward therapeutic applications. Vision restoration strategies using optogenetics are now at the forefront of these new clinical opportunities. But applications to human patients suffering from retinal diseases leading to blindness raise important concerns on the long-term functional expression of optogenes and the efficient signal transmission to higher visual centers. Here, we demonstrate in non-human primates continued expression and functionality at the retina level ∼20 months after delivery of our construct. We also performed in vivo recordings of visually evoked potentials in the primary visual cortex of anesthetized animals. Using synaptic blockers, we isolated the in vivo cortical activation resulting from the direct optogenetic stimulation of primate retina. In conclusion, our work indicates long-term transgene expression and transmission of the signal generated in the macaque retina to the visual cortex, two important features for future clinical applications. [Display omitted] The results we present here address two important concerns for vision restoration through optogenetic therapy: long-term expression and information transmission to higher visual areas. We demonstrate in non-human primates the longest expression time yet reported (>20 months), with transmission to the cortex of the optogenetic signal generated in the retina.