TYPE Original Research
PUBLISHED 06 February 2023
DOI 10.3389/fncel.2023.1115703
OPEN ACCESS
EDITED BY
Dao-Qi Zhang,
Oakland University, United States
REVIEWED BY
Feng Pan,
Hong Kong Polytechnic University,
Hong Kong SAR, China
Ning Tian,
The University of Utah, United States
*CORRESPONDENCE
Maesoon Im
maesoon.im@kist.re.kr;
maesoon.im@gmail.com
SPECIALTY SECTION
This article was submitted to
Cellular Neurophysiology,
a section of the journal
Frontiers in Cellular Neuroscience
RECEIVED 04 December 2022
ACCEPTED 19 January 2023
PUBLISHED 06 February 2023
CITATION
Roh H, Otgondemberel Y, Eom J, Kim D and
Im M (2023) Electrically-evoked responses
for retinal prostheses are differentially altered
depending on ganglion cell types in outer
retinal neurodegeneration caused by Crb1
gene mutation.
Front. Cell. Neurosci. 17:1115703.
doi: 10.3389/fncel.2023.1115703
COPYRIGHT
© 2023 Roh, Otgondemberel, Eom, Kim and Im.
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Electrically-evoked responses for
retinal prostheses are differentially
altered depending on ganglion cell
types in outer retinal
neurodegeneration caused by Crb1
gene mutation
Hyeonhee Roh
1,2
, Yanjinsuren Otgondemberel
1
,
Jeonghyeon Eom
1,3
, Daniel Kim
1,4
and Maesoon Im
1,5
*
1
Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea,
2
School of
Electrical Engineering, Korea University, Seoul, Republic of Korea,
3
School of Electrical Engineering,
Kookmin University, Seoul, Republic of Korea,
4
Department of Biomedical Sciences, Seoul National
University College of Medicine, Seoul, Republic of Korea,
5
Division of Bio-Medical Science & Technology,
KIST School, University of Science and Technology, Seoul, Republic of Korea
Background: Microelectronic prostheses for artificial vision stimulate neurons
surviving outer retinal neurodegeneration such as retinitis pigmentosa (RP). Yet, the
quality of prosthetic vision substantially varies across subjects, maybe due to different
levels of retinal degeneration and/or distinct genotypes. Although the RP genotypes
are remarkably diverse, prosthetic studies have primarily used retinal degeneration
(rd) 1 and 10 mice, which both have Pde6b gene mutation. Here, we report the
electric responses arising in retinal ganglion cells (RGCs) of the rd8 mouse model
which has Crb1 mutation.
Methods: We first investigated age-dependent histological changes of wild-type
(wt), rd8, and rd10 mice retinas by H&E staining. Then, we used cell-attached patch
clamping to record spiking responses of ON, OFF and direction selective (DS) types
of RGCs to a 4-ms-long electric pulse. The electric responses of rd8 RGCs were
analyzed in comparison with those of wt RGCs in terms of individual RGC spiking
patterns, populational characteristics, and spiking consistency across trials.
Results: In the histological examination, the rd8 mice showed partial retinal foldings,
but the outer nuclear layer thicknesses remained comparable to those of the wt
mice, indicating the early-stage of RP. Although spiking patterns of each RGC type
seemed similar to those of the wt retinas, correlation levels between electric vs.
light response features were different across the two mouse models. For example,
in comparisons between light vs. electric response magnitudes, ON/OFF RGCs of
the rd8 mice showed the same/opposite correlation polarity with those of wt mice,
respectively. Also, the electric response spike counts of DS RGCs in the rd8 retinas
showed a positive correlation with their direction selectivity indices (r = 0.40), while
those of the wt retinas were negatively correlated (r = −0.90). Lastly, the spiking
timing consistencies of late responses were largely decreased in both ON and OFF
RGCs in the rd8 than the wt retinas, whereas no significant difference was found
across DS RGCs of the two models.
Conclusion: Our results indicate the electric response features are altered depending
on RGC types even from the early-stage RP caused by Crb1 mutation. Given the
Frontiers in Cellular Neuroscience 01 frontiersin.org