The long-term objectives of my research are to understand the visual signaling function of theretina and to exploit this knowledge for the treatment of blindness. The major goal of theproposed work is to develop techniques for precise, patterned multi-electrode stimulation of theretina, with the purpose of advancing the development of high-resolution retinal prostheticdevices 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 primateretina, as well as several ganglion cell types in the degenerating rat retina, (2) selectivelystimulating individual cells to achieve the elementary spatial and temporal resolution of normalvisual signals transmitted to the brain while avoiding stimulation of axons, over a range of retinaleccentricities, and (3) evoking spatial and spatiotemporal patterns of activity in populations ofganglion cells that can mimic the complex visual signals normally transmitted to the brain. Wewill apply our unique technology to simultaneously and independently stimulate and record frommany ganglion cells in vitro, using an array of electrodes comparable to but much smaller anddenser than those used in current retinal prosthetics. We will exploit this technology to developnew methods for focal and patterned stimulation to mimic visual signals, including developmentof novel technologies to target the central retina. We will also leverage our experience with theprimate retina and the P23H mutant rat model of retinal degeneration to maximize the relevanceof the findings for treating blindness. Our vision is that the work will aid the design of the nextgeneration of retinal prosthetic devices to support advanced visual functions such as objectrecognition and motion sensing in human patients.

Public Health Relevance

The goal of the proposed work is to advance the development of high-resolution retinalprosthetic devices to treat blindness; using electrophysiological recording and stimulation of theprimate and degenerating retina in vitro. Our approach leverages a specialized multi-electroderecording and stimulation technology designed to resemble future prosthetic devices; with anemphasis on emulating naturalistic visual signals and interfacing with the parallel pathways forhigh-resolution vision in primates. This unique approach will further the design of the nextgeneration of retinal prostheses -- devices that can support advanced visual functions such asobject recognition and motion sensing in human patients.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
7R01EY021271-04
Application #
8796029
Study Section
Central Visual Processing Study Section (CVP)
Program Officer
Greenwell, Thomas
Project Start
2014-05-01
Project End
2016-07-31
Budget Start
2014-05-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2013
Total Cost
$275,665
Indirect Cost
$88,047
Name
Stanford University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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