Short Pulse Epiretinal Stimulation Allows Focal Activation of Retinal Ganglion Cells

Epiretinal implants suffer from a lack of spatial resolution, which is greatly influenced by the undesired co-activation of distal cells with their axons passing close to targeted somas. Short current pulses in the range of <inline-formula> <tex-math notation="LaTeX">$50\mu $ &...

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Main Authors: Laurin X. Koppenwallner, Gunther Zeck, Paul Werginz
Format: Article
Language:English
Published: IEEE 2025-01-01
Series:IEEE Transactions on Neural Systems and Rehabilitation Engineering
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Online Access:https://ieeexplore.ieee.org/document/10843246/
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author Laurin X. Koppenwallner
Gunther Zeck
Paul Werginz
author_facet Laurin X. Koppenwallner
Gunther Zeck
Paul Werginz
author_sort Laurin X. Koppenwallner
collection DOAJ
description Epiretinal implants suffer from a lack of spatial resolution, which is greatly influenced by the undesired co-activation of distal cells with their axons passing close to targeted somas. Short current pulses in the range of <inline-formula> <tex-math notation="LaTeX">$50\mu $ </tex-math></inline-formula>s have been shown to preferentially activate somas, but the low specificity may limit practical applications. In this paper, we explored decreasing pulse durations down to <inline-formula> <tex-math notation="LaTeX">$10\mu $ </tex-math></inline-formula>s for achieving focal activation, i.e., a large differentiation between axonal and somatic activation in epiretinal configuration. We determined thresholds for pulses ranging between 10 and <inline-formula> <tex-math notation="LaTeX">$500\mu $ </tex-math></inline-formula>s in retinal ganglion cells of both wild-type and photoreceptor-degenerated mouse retina. Ex-vivo stimulation using biphasic rectangular pulses was performed using a custom-built modified Howland-type current-controlled stimulator and a microelectrode. We demonstrate reliable direct activation of retinal ganglion cells using <inline-formula> <tex-math notation="LaTeX">$10\mu $ </tex-math></inline-formula>s pulses for both somatic and axonal electrode positions. Cells from wild-type and photoreceptor-degenerated retinas exhibited similar thresholds. Axonal thresholds were significantly higher for all pulse durations, with the ratio between axonal and somatic thresholds strongly increasing with decreasing pulse duration (1.32 and 4.39 for pulse durations of 500 and <inline-formula> <tex-math notation="LaTeX">$10\mu $ </tex-math></inline-formula>s, respectively). Computational modeling points to somatic polarization as the underlying mechanism for lower somatic thresholds. Our results demonstrate focal activation with pulses in the range of <inline-formula> <tex-math notation="LaTeX">$10\mu $ </tex-math></inline-formula>s as a potential strategy to avoid the long-standing problem of axonal co-activation in epiretinal implants.
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spelling doaj-art-e41ea6114247438b86d16c64bbd350ce2025-01-29T00:00:03ZengIEEEIEEE Transactions on Neural Systems and Rehabilitation Engineering1534-43201558-02102025-01-013354255310.1109/TNSRE.2025.352994010843246Short Pulse Epiretinal Stimulation Allows Focal Activation of Retinal Ganglion CellsLaurin X. Koppenwallner0https://orcid.org/0009-0002-3157-5635Gunther Zeck1https://orcid.org/0000-0003-3998-9883Paul Werginz2https://orcid.org/0000-0002-3441-3167Institute of Biomedical Electronics, TU Wien, Vienna, AustriaInstitute of Biomedical Electronics, TU Wien, Vienna, AustriaInstitute of Biomedical Electronics, TU Wien, Vienna, AustriaEpiretinal implants suffer from a lack of spatial resolution, which is greatly influenced by the undesired co-activation of distal cells with their axons passing close to targeted somas. Short current pulses in the range of <inline-formula> <tex-math notation="LaTeX">$50\mu $ </tex-math></inline-formula>s have been shown to preferentially activate somas, but the low specificity may limit practical applications. In this paper, we explored decreasing pulse durations down to <inline-formula> <tex-math notation="LaTeX">$10\mu $ </tex-math></inline-formula>s for achieving focal activation, i.e., a large differentiation between axonal and somatic activation in epiretinal configuration. We determined thresholds for pulses ranging between 10 and <inline-formula> <tex-math notation="LaTeX">$500\mu $ </tex-math></inline-formula>s in retinal ganglion cells of both wild-type and photoreceptor-degenerated mouse retina. Ex-vivo stimulation using biphasic rectangular pulses was performed using a custom-built modified Howland-type current-controlled stimulator and a microelectrode. We demonstrate reliable direct activation of retinal ganglion cells using <inline-formula> <tex-math notation="LaTeX">$10\mu $ </tex-math></inline-formula>s pulses for both somatic and axonal electrode positions. Cells from wild-type and photoreceptor-degenerated retinas exhibited similar thresholds. Axonal thresholds were significantly higher for all pulse durations, with the ratio between axonal and somatic thresholds strongly increasing with decreasing pulse duration (1.32 and 4.39 for pulse durations of 500 and <inline-formula> <tex-math notation="LaTeX">$10\mu $ </tex-math></inline-formula>s, respectively). Computational modeling points to somatic polarization as the underlying mechanism for lower somatic thresholds. Our results demonstrate focal activation with pulses in the range of <inline-formula> <tex-math notation="LaTeX">$10\mu $ </tex-math></inline-formula>s as a potential strategy to avoid the long-standing problem of axonal co-activation in epiretinal implants.https://ieeexplore.ieee.org/document/10843246/Electrical stimulationretinal ganglion cellsretinal implantshort pulse stimulation
spellingShingle Laurin X. Koppenwallner
Gunther Zeck
Paul Werginz
Short Pulse Epiretinal Stimulation Allows Focal Activation of Retinal Ganglion Cells
IEEE Transactions on Neural Systems and Rehabilitation Engineering
Electrical stimulation
retinal ganglion cells
retinal implant
short pulse stimulation
title Short Pulse Epiretinal Stimulation Allows Focal Activation of Retinal Ganglion Cells
title_full Short Pulse Epiretinal Stimulation Allows Focal Activation of Retinal Ganglion Cells
title_fullStr Short Pulse Epiretinal Stimulation Allows Focal Activation of Retinal Ganglion Cells
title_full_unstemmed Short Pulse Epiretinal Stimulation Allows Focal Activation of Retinal Ganglion Cells
title_short Short Pulse Epiretinal Stimulation Allows Focal Activation of Retinal Ganglion Cells
title_sort short pulse epiretinal stimulation allows focal activation of retinal ganglion cells
topic Electrical stimulation
retinal ganglion cells
retinal implant
short pulse stimulation
url https://ieeexplore.ieee.org/document/10843246/
work_keys_str_mv AT laurinxkoppenwallner shortpulseepiretinalstimulationallowsfocalactivationofretinalganglioncells
AT guntherzeck shortpulseepiretinalstimulationallowsfocalactivationofretinalganglioncells
AT paulwerginz shortpulseepiretinalstimulationallowsfocalactivationofretinalganglioncells