Abstract
Patients with retinal degeneration lose sight due to the gradual demise of photoreceptors. Electrical stimulation of surviving retinal neurons provides an alternative route for the delivery of visual information. We demonstrate that subretinal implants with 70-μm-wide photovoltaic pixels provide highly localized stimulation of retinal neurons in rats. The electrical receptive fields recorded in retinal ganglion cells were similar in size to the natural visual receptive fields. Similarly to normal vision, the retinal response to prosthetic stimulation exhibited flicker fusion at high frequencies, adaptation to static images and nonlinear spatial summation. In rats with retinal degeneration, these photovoltaic arrays elicited retinal responses with a spatial resolution of 64 ± 11 μm, corresponding to half of the normal visual acuity in healthy rats. The ease of implantation of these wireless and modular arrays, combined with their high resolution, opens the door to the functional restoration of sight in patients blinded by retinal degeneration.
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Acknowledgements
We would like to thank D. Boinagrov, E.J. Chichilnisky, M.F. Marmor and S. Picaud for stimulating discussions and encouragement. We would also like to thank J. Liao for providing the VEP recording setup, S. Lee for assistance in developing surgical procedures, as well as P. Haeusser, S. Kachiguine, P. Hottowy and A. Litke for providing and supporting the multielectrode array recording setup. Funding was provided by the US National Institutes of Health (grant R01-EY-018608, D.P.), the Department of Defense (grant W81XWH-15-1-0009, D.P.) and the Stanford Spectrum fund (D.P.). A.S. was supported by a Burroughs Wellcome Fund Career Award at the Scientific Interface and a Pew Charitable Trusts Scholarship in the Biomedical Sciences. K.M. was supported by an SU2P fellowship as part of a RCUK Science Bridges award. H.L. was supported by the Foundation Voir et Entendre (Paris) and Pixium Vision.
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X.L. fabricated the subretinal implants under the supervision of T.K., K.M., J.H. and D.P. G.G., R.S., D.P. and A.S. designed the in vitro experiments. R.S. and G.G. performed the in vitro experiments. H.L., D.P. and Y.M. designed the in vivo experiments. H.L., Y.M. and P.H. performed the in vivo experiments. G.G. and H.L. analyzed the data. G.G., H.L., A.S. and D.P. wrote the paper.
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D.P.'s patents related to retinal prosthesis are owned by Stanford University and licensed to Pixium Vision. D.P. is a consultant for Pixium Vision.
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Lorach, H., Goetz, G., Smith, R. et al. Photovoltaic restoration of sight with high visual acuity. Nat Med 21, 476–482 (2015). https://doi.org/10.1038/nm.3851
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DOI: https://doi.org/10.1038/nm.3851
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