Project Summary/Abstract The goal of our work is to advance the development of high-resolution epiretinal prosthetic devices for treating incurable blindness from retinal degeneration. We approach this by developing novel techniques for high-resolution, multi-electrode stimulation of retinal ganglion cells in the isolated retina, as a laboratory platform for developing the necessary approaches for restoring vision. The major goals of this project are to (1) develop methods to detect and avoid the unintended activation of axon bundles that corrupts the artificial image, (2) develop methods to efficiently stimulate specific cells and cell types while avoiding stimulation of other cells, and (3) develop spatiotemporally patterned stimulation and high-density recording and stimulation for use in the central retina, which is necessary for high-resolution vision. Tackling these aims is anticipated to support the development of a device that can emulate the neural code of the retina, cell-by-cell and spike-by-spike, over a substantial area. The unique technical approach employed involves large-scale, high-resolution electrical recording and stimulation, combined with novel analysis, imaging, and computational approaches to optimize the artificial visual signal. Our vision is that this work will aid the design of the next generation of retinal prosthetic devices to support advanced visual functions, such as object recognition and motion sensing, in human patients.