Feasibility of an Optogenetic Prosthesis for the Primate Eye

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Abstract Photoreceptors and retinal pigment epithelium (RPE) cells in the outer retina are highly vulnerable to degenerative eye disease, but recent advances in optogenetics offer the possibility of restoring vision after loss of photoreceptor function. This approach has been demonstrated already in the mouse. This project will deploy a monkey model to explore the feasibility of a retinal prosthetic that bypasses degenerated photoreceptors by using optogenetic methods to make retinal ganglion cells light-sensitive. The monkey model is needed because the monkey has a fovea and human-like visual perception. To establish a monkey model of retinal degeneration, we will use phototoxicity to selectively destroy photoreceptors in localized retinal areas following exposure to bright light. We will then attempt to restore light sensitivity by transducing ganglion cells with an intravitreal injection of a viral vector designed to express channelrhodopsin. We will evaluate both the effectiveness of the light exposure in destroying photoreceptor function and the effectiveness of the optogenetic prosthesis in restoring function with two methods. First, we will measure the light responses of ganglion cells with a genetically encoded calcium indicator, imaged in the living eye with adaptive optics. The method will allow us to track ganglion cell function repeatedly over many weeks in the same monkey. Second, we will measure the visual effectiveness of the optogenetic prosthetic with visual psychophysical tasks. If these experiments are successful, they will clarify the photosensitivity, dynamic range, and information capacity of an optogenetic prosthetic applied to the primate fovea.