Prosthetic electrical stimulation of inner retinal neurons can restore a sense of vision in patients with outer retinal degeneration, but implant patients to date report artificial vision to be low quality. Clinical studies of retinal prostheses show that long-term implantation and stimulation is safe, and that implant patients can detect large objects and recognize simple forms. But visual acuity is 20/438 at best, and functional vision is limited by rapid (within seconds) fading of electrically elicited percepts. Numerous clinical and animal studies demonstrate that current approaches for retinal stimulation cannot activate the retina with adequate spatial specificity to produce high quality vision. Thus, the research team proposes to advance several innovative technical approaches that will have the combined effect of substantially improving both spatial resolution and temporal control of evoked responses. When implemented clinically, a retinal prosthesis incorporating the proposed technology is expected to achieve 20/160 vision. Current retinal prostheses have numerous drawbacks. Epiretinal implants have planar electrodes on the retinal surface, which often activate retinal ganglion cell (RGC) axons-of-passage. Consequently, RGC axons with receptive fields far from the stimulation sites are unintentionally excited, resulting in elongated percepts. Epiretinal electrodes tend to gradually separate from the retina, which also increases the charge threshold. Suprachoroidal implants likewise have limited resolution due to the large currents needed to bridge the distance across the choroid separating the electrode array and retina. Subretinal implants reduce the electrode-retina distance and preferentially stimulate bipolar cells, avoiding RGC axons, thus achieving better visual acuity than epiretinal implants. But photovoltaic subretinal implants that lack pulse timing circuitry use simultaneous stimulation, resulting in overlapping electronic receptive fields and reduced spatial resolution. Subretinal implants with extraocular cables can interleave stimulation to avoid simultaneous stimulation, but such cables complicate surgery. In practice, subretinal implants can only be applied to a small part of the visual field since implantation requires retinal detachment, thus limiting their effectiveness in treating retinitis pigmentosa, which causes wide-field vision loss. The research team’s overarching hypothesis is that intraretinal electrodes positioned within the inner nuclear layer can overcome all the above limitations. To test this hypothesis, the team will define the mechanism of intraretinal stimulation by measuring RGC responses, optimize the resolution of multichannel intraretinal stimulation using computational approaches to parameter selection and tuning, and verify long-term functionality and biocompatibility of a high-density carbon fiber array. With expertise in neural engineering, retinal neurobiology, and retinal surgery, the project...