The long-term objectives of my research are to understand the visual signaling function of the retina and to exploit this knowledge for the treatment of blindness. The major goal of the proposed work is to develop techniques for precise, patterned multi-electrode stimulation of the retina, with the purpose of advancing the development of high-resolution retinal prosthetic devices to replace the function of retinas damaged by degeneration.
The specific aims i nvolve (1) evoking electrical activity in the major high-resolution ganglion cell types of the primate retina, as well as several ganglion cell types in the degenerating rat retina, (2) selectively stimulating individual cells to achieve the elementary spatial and temporal resolution of normal visual signals transmitted to the brain while avoiding stimulation of axons, over a range of retinal eccentricities, and (3) evoking spatial and spatiotemporal patterns of activity in populations of ganglion cells that can mimic the complex visual signals normally transmitted to the brain. We will apply our unique technology to simultaneously and independently stimulate and record from many ganglion cells in vitro, using an array of electrodes comparable to but much smaller and denser than those used in current retinal prosthetics. We will exploit this technology to develop new methods for focal and patterned stimulation to mimic visual signals, including development of novel technologies to target the central retina. We will also leverage our experience with the primate retina and the P23H mutant rat model of retinal degeneration to maximize the relevance of the findings for treating blindness. Our vision is that the 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.

Public Health Relevance

The goal of the proposed work is to advance the development of high-resolution retinal prosthetic devices to treat blindness, using electrophysiological recording and stimulation of the primate and degenerating retina in vitro. Our approach leverages a specialized multi-electrode recording and stimulation technology designed to resemble future prosthetic devices, with an emphasis on emulating naturalistic visual signals and interfacing with the parallel pathways for high-resolution vision in primates. This unique approach will further the design of the next generation of retinal prostheses -- devices that can support advanced visual functions such as object recognition and motion sensing in human patients.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Central Visual Processing Study Section (CVP)
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Greenwell, Thomas
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Stanford University
Schools of Medicine
United States
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Ravi, Sneha; Ahn, Daniel; Greschner, Martin et al. (2018) Pathway-Specific Asymmetries between ON and OFF Visual Signals. J Neurosci 38:9728-9740
Grosberg, Lauren E; Ganesan, Karthik; Goetz, Georges A et al. (2017) Activation of ganglion cells and axon bundles using epiretinal electrical stimulation. J Neurophysiol 118:1457-1471
Jepson, Lauren H; Hottowy, Pawe?; Mathieson, Keith et al. (2014) Spatially patterned electrical stimulation to enhance resolution of retinal prostheses. J Neurosci 34:4871-81
Jepson, Lauren H; Hottowy, Pawel; Weiner, Geoffrey A et al. (2014) High-fidelity reproduction of spatiotemporal visual signals for retinal prosthesis. Neuron 83:87-92
Jepson, Lauren H; Hottowy, Pawel; Mathieson, Keith et al. (2013) Focal electrical stimulation of major ganglion cell types in the primate retina for the design of visual prostheses. J Neurosci 33:7194-205
Sekirnjak, Chris; Jepson, Lauren H; Hottowy, Pawel et al. (2011) Changes in physiological properties of rat ganglion cells during retinal degeneration. J Neurophysiol 105:2560-71