Probing visual computations and electrical stimulation in the central macaque retina for high fidelity vision restoration

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Project Summary/Abstract Blindness resulting from photoreceptor degeneration is a leading cause of disability. A primary treatment option is the use of epiretinal prostheses, which directly activate retinal ganglion cells (RGCs), sending artificial visual signals to the brain. However, vision restoration with current-day epiretinal prostheses is limited, due to the coarse-grained stimulation that fails to replicate natural, light-evoked RGC activation patterns. In natural vision, ~20 functionally-distinct RGC types communicate unique representations of the visual world to the brain through coordinated and precise cell type-specific patterns of activity. Modern implants don’t produce high-acuity vision in part because they fail to elicit naturalistic RGC responses, due to coarse and nonspecific stimulation. The goal of my research is to determine how well vision can be restored in the central retina by analyzing the responses of primate RGCs to visual and electrical stimulation. To accomplish this goal, I will first conduct ex vivo experiments in the central retina of the macaque monkey with visual and electrical stimulation while recording with a high-density multi-electrode array. After identifying the major functionally-distinct cell types, we will then characterize their spatiotemporal light response properties and determine how they differ from cells of the same types in the peripheral retina. I will also compare how well features from natural images are represented by central and peripheral RGCs of the major types. Next, to determine how well central RGCs can be electrically activated, I will determine the electrical receptive fields for each cell as well as quantify the extent to which RGCs of each type can be stimulated selectively. We will then test the degree to which RGCs of major types in the central retina can be activated without activating axon bundles. To achieve better electrical access to RGCs in the central retina, I will test whether removing the inner limiting membrane decreases stimulation thresholds and enhances selective activation. In cases in which selective activation of RGCs is unattainable with single-electrode stimulation, I will test whether tri-electrode stimulation can better focus the electric field on a cell of interest through current steering to enhance selective activation. Finally, to estimate how well high-resolution vision can be restored with a future implant targeting the central retina, we will develop a simulation by aggregating the visual and electrical response properties across many data sets and perform image reconstruction analyses to quantify the structural details of images that can be perceived.