Retinal prostheses for the blind have shown encouraging results. Blind patients implanted with devices have improved mobility and better performance in visually guided tasks. The ability to perceive complex shapes has been difficult for manyh implant patients. Recent psychophysics testing has shown that many single- electrode percepts are elongated, extending beyond what would be expected if only the retina near the electrode were activated. These results, coupled with calcium imaging experiments in in vitro retina, suggest more extensive axonal stimulation than previously believed. Axonal stimulation may result in elongated perceptions created not only by the retinal ganglion cells under the electrode, but also by the retinal ganglion cells distl to the electrode, but whose axons pass under the electrode. A series of studies have found that long-duration stimuli may target selectively inner retina neurons and avoid activation of axons. Preliminary data in support of this proposal shows that 20-Hz sine wave stimulation elicited a focal response in in vitro rat retina and in a human with a retinal prosthesis implant. The in vito data was recorded using a novel adeno-associated viral vector that transduces retinal ganglion cells such that the cells express an intracellular calcium indicator, GCaMP. The preliminary results suggest that in vitro retina is an excellent model for human perception. The proposed Bioengineering Research Partnership will thoroughly investigate the predictive power of in vitro retina as it relates to shape perception in humans. Novel stimulus protocols will be developed using in vitro retina. Unique retinal imaging techniques will allow unprecedented measurements of the spatial extent of electrically elicited responses from the retina. Electrophysiolgical recordings from single cells will complement and validate the imaging data. Responses to single and multi-electrode stimulation will be measured. Promising stimuli will be tested in humans with retinal implants. The significance of the proposed research is thus two-fold. First, we will advance shape perception in patients with retinal implants, by identifying optimal stimulus protocols. Secondly, and more broadly, we will establish in vitro retina as tool to infor the design of future implants that promise higher acuity vision.

Public Health Relevance

Retinitis pigmentosa and age-related macular degeneration are two significant causes of blindness. Microelectronic retinal prostheses have the potential to restore partial vision to patients with these diseases. The proposed research will investigate methods for improving the visual capability of current implant patients and optimizing the design of next generation implants. See Research Strategy section for more detailed information.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-ETTN-B (51))
Program Officer
Greenwell, Thomas
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Southern California
Schools of Medicine
Los Angeles
United States
Zip Code
Lin, Ming-Yi; Wang, Yi-Ling; Wu, Wan-Lin et al. (2017) Zika Virus Infects Intermediate Progenitor Cells and Post-mitotic Committed Neurons in Human Fetal Brain Tissues. Sci Rep 7:14883
Cho, Jung-Hwa; Swanson, Carter J; Chen, Jeannie et al. (2017) The GCaMP-R Family of Genetically Encoded Ratiometric Calcium Indicators. ACS Chem Biol 12:1066-1074
Weiland, James D; Walston, Steven T; Humayun, Mark S (2016) Electrical Stimulation of the Retina to Produce Artificial Vision. Annu Rev Vis Sci 2:273-294
Cho, Alice; Ratliff, Charles; Sampath, Alapakkam et al. (2016) Changes in ganglion cell physiology during retinal degeneration influence excitability by prosthetic electrodes. J Neural Eng 13:025001
Gonzalez-Calle, A; Weiland, J D (2016) Evaluation of Effects of Electrical Stimulation in the Retina with Optical Coherence Tomography. Conf Proc IEEE Eng Med Biol Soc 2016:6182-6185
Chang, Yao-Chuan; Walston, Steven T; Chow, Robert H et al. (2016) In vivo characterization of genetic expression of virus-transduced calcium indicators in retinal ganglion cells using a low-cost funduscope. Conf Proc IEEE Eng Med Biol Soc 2016:1316-1319
Weitz, Andrew C; Nanduri, Devyani; Behrend, Matthew R et al. (2015) Improving the spatial resolution of epiretinal implants by increasing stimulus pulse duration. Sci Transl Med 7:318ra203
Walston, Steven T; Chow, Robert H; Weiland, James D (2015) Patch clamp recordings of retinal bipolar cells in response to extracellular electrical stimulation in wholemount mouse retina. Conf Proc IEEE Eng Med Biol Soc 2015:3363-6
Weiland, James D; Humayun, Mark S (2014) Retinal prosthesis. IEEE Trans Biomed Eng 61:1412-24
Weitz, Andrew C; Behrend, Matthew R; Ahuja, Ashish K et al. (2014) Interphase gap as a means to reduce electrical stimulation thresholds for epiretinal prostheses. J Neural Eng 11:016007

Showing the most recent 10 out of 11 publications