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Functional development of photoreceptors in human retinal organoids.

Overview

Authors: Yue Zhang1,2, Mingxia Du1,2, Yi-Han Wang1,2, Min Li1,2, Kangxin Jin1,2, Deng Pan1,2, Xiao Zhang1,2, Zi-Bing Jin1,2
  1. Beijing Institute of Ophthalmology, Department of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory for Ophthalmic Cell and Gene Therapy, Beijing, 100008 China
  2. Laboratory for Clinical Medicine, Capital Medical University, Beijing, 100069 China
Institutions: Beijing Tongren Hospital (China); Capital Medical University (China)
Journal: Stem cell research & therapy, volume 17, issue 1, article 223
Dates: received 24 October 2025; accepted 12 April 2026; published online 30 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1186/s13287-026-05027-z · PMID 42063112 · PMCID PMC13277147 · OpenAlex W7159627604
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: intracellular / patch clamp (modality), human (organism)
Methods: Statistics, fMRI & imaging
Keywords: Retinal organoids, hESC, Whole-cell patch-clamp, Photoreceptor, Ion channel
MeSH: Organoids*, Photoreceptor Cells*, Retina*, Action Potentials, Cell Differentiation, Human Embryonic Stem Cells, Humans, Patch-Clamp Techniques (* major topic)
Topic: Retinal Development and Disorders (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: National Natural Science Foundation of China (82201225, 82125007); Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes (PWD&RPP-MRI, PWD&RPP-MRI, JYY2023-6); Excellent Clinical Research Program (BRWEP2024W172050100); Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (DFL20220202); Beijing Municipal Science & Technology Commission (Z231100007223005); Beijing Natural Science Foundation (Z200014); Beijing Municipal Science & Technology Commission (Z231100007223005)
Citations: cited by 1 paper (Europe PMC); 61 references in the paper

Abstract

Background: Retinal organoids (ROs) derived from human pluripotent stem cells are crucial for modeling retinal development and disease. However, the functional electrophysiological maturation of photoreceptors within ROs remains poorly characterized. This study aimed to define the functional maturation timeline of photoreceptors in human embryonic stem cell (hESC)-derived ROs.

Methods: H9 hESC-derived ROs which included a CRX-tdTomato reporter line for specific photoreceptor identification were utilized. An integrated approach of RNA-sequencing analysis, immunofluorescence staining, and whole-cell patch-clamp recordings was employed to systematically assess photoreceptor maturation over 300 days of differentiation.

Results: Transcriptional and protein analysis revealed progressive upregulation of key ion channels. Patch-clamp recordings demonstrated stage-dependent maturation of membrane properties, which stabilized by D120–125. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated currents (Ih) increased progressively, peaking at D240, with amplitudes comparable to mature primate photoreceptors. Voltage-gated sodium (Nav) currents also showed significant developmental upregulation, reaching a maximum, stable plateau from D210–215 onward. Pharmacological blockade confirmed the identity of HCN and Nav currents. Critically, the capacity for action potential (AP) generation increased developmentally, with the proportion of photoreceptors capable of firing APs rising from 16.7% at D90–95 to a peak of 90.2% by D240–245.

Conclusions: This study defines a comprehensive electrophysiological maturation timeline for photoreceptors in human ROs and establishes D240 as a key benchmark for functional maturity, characterized by peak Ih currents and AP generation capacity equivalent to mature native photoreceptors. These findings provide essential physiological criteria for standardizing RO quality control, enhancing their utility for modeling retinal degenerative diseases and developing cell replacement therapies.

Supplementary Information: The online version contains supplementary material available at10.1186/s13287-026-05027-z.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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The data that support the findings of this study are available within the article and its supplementary materials.

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 5 keywords, 8 MeSH terms, 7 funders, 61 references.

Cite

This paper

Zhang, Y., Du, M., Wang, Y.-H., Li, M., Jin, K., Pan, D., Zhang, X., & Jin, Z.-B. (2026). Functional development of photoreceptors in human retinal organoids. Stem cell research & therapy, 17(1), 223. https://doi.org/10.1186/s13287-026-05027-z

BibTeX

@article{zhang2026functional,
author = {Zhang, Yue and Du, Mingxia and Wang, Yi-Han and Li, Min and Jin, Kangxin and Pan, Deng and Zhang, Xiao and Jin, Zi-Bing},
title = {{Functional development of photoreceptors in human retinal organoids}},
journal = {Stem cell research \& therapy},
year = {2026},
month = apr,
volume = {17},
number = {1},
pages = {223},
publisher = {BMC},
issn = {1757-6512},
doi = {10.1186/s13287-026-05027-z},
url = {https://doi.org/10.1186/s13287-026-05027-z},
pmid = {42063112},
pmcid = {PMC13277147}
}

RIS

TY - JOUR
AU - Zhang, Yue
AU - Du, Mingxia
AU - Wang, Yi-Han
AU - Li, Min
AU - Jin, Kangxin
AU - Pan, Deng
AU - Zhang, Xiao
AU - Jin, Zi-Bing
TI - Functional development of photoreceptors in human retinal organoids
T2 - Stem cell research & therapy
J2 - Stem Cell Res Ther
PY - 2026
DA - 2026/04/30
VL - 17
IS - 1
SP - 223
SN - 1757-6512
PB - BMC
DO - 10.1186/s13287-026-05027-z
UR - https://doi.org/10.1186/s13287-026-05027-z
LA - en
ER -

CSL-JSON

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