Cone photoreceptors in human stem cell-derived retinal organoids demonstrate intrinsic light responses that mimic those of primate fovea.
cone photoreceptors
fovea
macaque
macular degeneration
organoid development
phototransduction
pluripotent stem cell
primate retina
retinal organoid
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
03 03 2022
03 03 2022
Historique:
received:
24
05
2021
revised:
11
11
2021
accepted:
04
01
2022
pubmed:
2
2
2022
medline:
19
4
2022
entrez:
1
2
2022
Statut:
ppublish
Résumé
High-definition vision in humans and nonhuman primates is initiated by cone photoreceptors located within a specialized region of the retina called the fovea. Foveal cone death is the ultimate cause of central blindness in numerous retinal dystrophies, including macular degenerative diseases. 3D retinal organoids (ROs) derived from human pluripotent stem cells (hPSCs) hold tremendous promise to model and treat such diseases. To achieve this goal, RO cones should elicit robust and intrinsic light-evoked electrical responses (i.e., phototransduction) akin to adult foveal cones, which has not yet been demonstrated. Here, we show strong, graded, repetitive, and wavelength-specific light-evoked responses from RO cones. The photoresponses and membrane physiology of a significant fraction of these lab-generated cones are comparable with those of intact ex vivo primate fovea. These results greatly increase confidence in ROs as potential sources of functional human cones for cell replacement therapies, drug testing, and in vitro models of retinal dystrophies.
Identifiants
pubmed: 35104442
pii: S1934-5909(22)00002-9
doi: 10.1016/j.stem.2022.01.002
pmc: PMC9093561
mid: NIHMS1776777
pii:
doi:
Substances chimiques
Reactive Oxygen Species
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
460-471.e3Subventions
Organisme : NEI NIH HHS
ID : R00 EY026070
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD090256
Pays : United States
Organisme : NIH HHS
ID : P51 OD011106
Pays : United States
Organisme : NEI NIH HHS
ID : U24 EY029890
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY031411
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests D.M.G. is an inventor on patents related to generation of 3D retinal organoids (US PTO no. 9,328,328) filed by the Wisconsin Alumni Research Foundation, Madison, WI. D.M.G. has an ownership interest in and receives grant funding from Opsis Therapeutics, LLC, which has licensed the technology to generate 3D retinal organoids. The terms of this arrangement have been reviewed and approved by the University of Wisconsin-Madison in accordance with its conflict-of-interest policies.
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