Despite the current enthusiasm for optogenetic vision restoration, there is remarkably little direct evidence about whether it can reverse blindness in humans. The feasibility of optogenetics was first suggested by studies from many labs that showed restoration of neuronal visual responses and visually guided behaviors in previously blind mice or dogs. These studies have been very informative in exploring interventions to treat retinal diseases genetically identical to some human disorders. However, they have not addressed restoration in an animal model that closely matches human vision, nor have they examined the perceptual quality of the restored vision. In the studies proposed here, we will address these two issues, first by using macaque monkeys in all studies, the animal model that most resembles humans in visual structure and function, and second by examining the range of visual perceptual abilities made possible by optogenetics. We will use a recently developed in-vivo physiology method to study vision restoration at the level of individual retinal cells in macaque monkeys. This approach will be used in the first aim to examine at a cellular level the spatial, temporal and sensitivity responses of macaque retinal neurons produced by optogenetic restoration. In the second aim we will use controlled fixation psychophysical testing of macaques to examine the range of visual capabilities provided by channelrhodopsin restoration, something that has never been studied. Finally, we will examine the duration of optogenetic restoration, measuring any long-term decrease in function or practice-related improvement in visual function.
The goal of this research is examine optogenetically restored vision in non- human primates to guide future restoration of vision in blind humans. We will use in-vivo adaptive optics imaging and controlled fixation psychophysical methods in macaque to examine visual responses provided by ganglion cell and ON bipolar cell optogenetics, something that has never been accomplished. We will also use psychophysical methods to study the duration of optogenetic restoration in macaques, examining the possibility of either degraded restoration or improved visual performance as the monkeys learn to use the restored visual signals.
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