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Original Article

Korean J Physiol Pharmacol 2023; 27(6): 541-553

Published online November 1, 2023

Copyright © Korean J Physiol Pharmacol.

Multiple consecutive-biphasic pulse stimulation improves spatially localized firing of retinal ganglion cells in the degenerate retina

Jungryul Ahn1, Yongseok Yoo2,*, and Yong Sook Goo1,*

1Department of Physiology, Chungbuk National University School of Medicine, Cheongju 28644, 2School of Computer Science and Engineering, Soongsil University, Seoul 06978, Korea

Correspondence to:Yongseok Yoo
Yong Sook Goo

Author contributions: J.A. conceptualization, methodology, data collection, formal analysis and investigation, writing - original draft preparation, writing - review and editing, funding acquisition. Y.Y. conceptualization, writing - review and editing. Y.S.G. conceptualization, writing - review and editing, funding acquisition. All authors approved the final manuscript.

Received: June 26, 2023; Revised: August 8, 2023; Accepted: August 22, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Retinal prostheses have shown some clinical success in restoring vision in patients with retinitis pigmentosa. However, the post-implantation visual acuity does not exceed that of legal blindness. The reason for the poor visual acuity might be that (1) degenerate retinal ganglion cells (RGCs) are less responsive to electrical stimulation than normal RGCs, and (2) electrically-evoked RGC spikes show a more widespread not focal response. The single-biphasic pulse electrical stimulation, commonly used in artificial vision, has limitations in addressing these issues. In this study, we propose the benefit of multiple consecutive-biphasic pulse stimulation. We used C57BL/6J mice and C3H/HeJ (rd1) mice for the normal retina and retinal degeneration model. An 8 × 8 multi-electrode array was used to record electrically-evoked RGC spikes. We compared RGC responses when increasing the amplitude of a single biphasic pulse versus increasing the number of consecutive biphasic pulses at the same stimulus charge. Increasing the amplitude of a single biphasic pulse induced more RGC spike firing while the spatial resolution of RGC populations decreased. For multiple consecutive-biphasic pulse stimulation, RGC firing increased as the number of pulses increased, and the spatial resolution of RGC populations was well preserved even up to 5 pulses. Multiple consecutive-biphasic pulse stimulation using two or three pulses in degenerate retinas induced as much RGC spike firing as in normal retinas. These findings suggest that the newly proposed multiple consecutive-biphasic pulse stimulation can improve the visual acuity in prosthesis-implanted patients.

Keywords: Electrically-evoked spikes, Multiple consecutive-biphasic pulse stimulation, Retinal degeneration, Retinal ganglion cell, Retinal prosthesis