Focal electrical stimulation of human retinal ganglion cells for vision restoration
Open accessPublished version of a preprint
Abstract
Abstract Objective . Vision restoration with retinal implants is limited by indiscriminate simultaneous activation of many cells and cell types, which is incompatible with reproducing the neural code of the retina. Recent work has shown that primate retinal ganglion cells (RGCs), which transmit visual information to the brain, can be directly electrically activated with single-cell, single-spike, cell-type precision – however, this possibility has never been tested in the human retina. In this study we aim to characterize, for the first time, direct in situ extracellular electrical stimulation of individual human RGCs. Approach . Extracellular electrical stimulation of individual human RGCs was conducted in three human retinas ex vivo using a custom large-scale, multi-electrode array capable of simultaneous recording and stimulation. Measured activation properties were compared directly to extensive results from macaque. Main results . Precise activation was in many cases possible without activating overlying axon bundles, at low stimulation current levels similar to those used in macaque. The major RGC types could be identified and targeted based on their distinctive electrical signatures. The measured electrical activation properties of RGCs, combined with a dynamic stimulation algorithm, was sufficient to produce an evoked visual signal that was nearly optimal given the constraints of the interface. Significance . These results suggest the possibility of high-fidelity vision restoration in humans using bi-directional epiretinal implants.
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The physiological similarities between human and macaque retina, including their responses to electrical stimulation, suggest that the benefits of the present stimulation approach could translate from the ex vivo lab prototype with healthy macaque retina to an in vivo implant in the degenerated human retina.
“The physiological similarities between human and macaque retina (Cowan et al., 2019; Kling et al., 2020; Soto et al., 2020; Rodieck, 1998), including their responses to electrical stimulation (Madugula et al., 2022), suggest that the benefits of the present stimulation approach could translate from the ex vivo lab prototype with healthy macaque retina to an in vivo implant in the degenerated human”
From Precise control of neural activity using dynamically optimized electrical stimulation (2024) · cites this paper as Madugula et al., 2022
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References 51 · Cited by 26
Research works printed but not linked: 5
- Dacey Dennis M. 2004. “ Origins of Perception: Retinal Ganglion Cell Diversity and the Creation of Parallel Visual Pathways.” In The Cognitive Neurosciences, 3: 281– 301. MIT Press, Cambridge.
- Rieke F, Warland D, de RR van Steveninck Ruyter, and Bialek W. 1997. Spikes: Exploring the Neural Code. Cambridge, MA: MIT Press.
- Rodieck RW 1998. The First Steps in Seeing. New York, NY: Oxford University Press.
- Sekirnjak Chris, Hottowy Pawel, Sher Alexander, Dabrowski Wladyslaw, Litke Alan M., and Chichilnisky EJ. 2008b. “ High-Resolution Electrical Stimulation of Primate Retina for Epiretinal Implant Design.” The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 28 (17): 4446– 56. 18434523 PMC2681084
- Wandell Brian A. 1995. Foundations of Vision. Oxford University Press, Incorporated.
- Authors
- Madugula, S. S., Gogliettino, A. R., Zaidi, M., Aggarwal, G., Kling, A., Shah, N. P., Brown, J. B., Vilkhu, R., Hays, M. R., Nguyen, H., Fan, V., Wu, E. G., Hottowy, P., Sher, A., Litke, A. M., Silva, R. A., & Chichilnisky, E. J.
- Affiliations
- Stanford Medicine (US)
- Stanford University (US)
- Faculty of Physics and Applied Computer Science, AGH University of Science and Technology
- University of California, Santa Cruz (US)
- Corresponding author
- Madugula, Sasidhar S
- Gogliettino, Alex R
- Zaidi, Moosa
- Aggarwal, Gorish
- Kling, Alexandra
- Shah, Nishal P
- Brown, Jeff B
- Vilkhu, Ramandeep
- Hays, Madeline R
- Nguyen, Huy
- Fan, Victoria
- Wu, Eric G
- Sher, Alexander
- Litke, Alan M
- Silva, Ruwan A
- Chichilnisky, E J
- ORCID
- Venue
- Journal of Neural Engineering
- Publisher
- IOP Publishing
- Published
- 2022-12-01
- Volume
- 19
- Issue
- 6
- Pages
- 066040
- ISSN
- 1741-2552 (ISSN-L)
- 1741-2560
- PMC
- PMC10010036
- OpenAlex
- W4309905341
- Cited by
- 26
- References
- 51
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 9 · 2023: 8 · 2021: 2
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Journal of Neural Engineering (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (F30-EY030776-03)
- John Chen (Donation)
- Polish National Science Centre (DEC-2013/10/M/NZ4/00268)
- Stanford University School of Medicine (Discovery Innovation Award)
- Wu Tsai Neurosciences Institute (Big Ideas)
- Pew Charitable Trusts (Scholarship in the Biomedical Sciences)
- Research to Prevent Blindness (Stein Innovation Award)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Tactile and Sensory Interactions
- Keywords
- retinal ganglion cells, focal electrical stimulation, vision restoration, retinal prosthesis, epiretinal implants, microelectrode arrays, cell type specificity
- MeSH terms
- Action Potentials, Animals, Electric Stimulation, Electrodes, Humans, Macaca, Photic Stimulation, Retina, Retinal Ganglion Cells, Visual Prosthesis
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