Characterization and staging of outer plexiform layer development in human retina and retinal organoids.

Bipolar cell Human fetal retina Human retinal organoid Outer plexiform layer Photoreceptor Ribbon synapse

Journal

Development (Cambridge, England)
ISSN: 1477-9129
Titre abrégé: Development
Pays: England
ID NLM: 8701744

Informations de publication

Date de publication:
01 12 2021
Historique:
received: 07 07 2021
accepted: 26 10 2021
pubmed: 6 11 2021
medline: 3 2 2022
entrez: 5 11 2021
Statut: ppublish

Résumé

The development of the first synapse of the visual system between photoreceptors and bipolar cells in the outer plexiform layer (OPL) of the human retina is crucial for visual processing but poorly understood. By studying the maturation state and spatial organization of photoreceptors, depolarizing bipolar cells and horizontal cells in the human fetal retina, we establish a pseudo-temporal staging system for OPL development that we term OPL-Stages 0 to 4. This was validated through quantification of increasingly precise subcellular localization of bassoon to the OPL with each stage (P<0.0001). By applying these OPL staging criteria to human retinal organoids (HROs) derived from human embryonic and induced pluripotent stem cells, we observed comparable maturation from OPL-Stage 0 at day 100 in culture up to OPL-Stage 3 by day 160. Quantification of presynaptic protein localization confirmed progression from OPL-Stage 0 to 3 (P<0.0001). Overall, this study defines stages of human OPL development through mid-gestation and establishes HROs as a model system that recapitulates key aspects of human photoreceptor-bipolar cell synaptogenesis in vitro.

Identifiants

pubmed: 34738615
pii: 272710
doi: 10.1242/dev.199551
pmc: PMC8714069
pii:
doi:

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

Subventions

Organisme : NEI NIH HHS
ID : K08 EY030924
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY026661
Pays : United States

Informations de copyright

© 2021. Published by The Company of Biologists Ltd.

Déclaration de conflit d'intérêts

Competing interests The authors declare no competing or financial interests.

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Auteurs

Sumitha Prameela Bharathan (S)

Department of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.

Angela Ferrario (A)

Department of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.

Kayla Stepanian (K)

Department of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.

G Esteban Fernandez (GE)

The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.

Mark W Reid (MW)

Department of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.

Justin S Kim (JS)

Department of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.

Chloe Hutchens (C)

Department of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.

Narine Harutyunyan (N)

Department of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.

Carolyn Marks (C)

Core Center of Excellence in Nano Imaging, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.

Matthew E Thornton (ME)

Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

Brendan H Grubbs (BH)

Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

David Cobrinik (D)

Department of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
Department of Ophthalmology, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

Jennifer G Aparicio (JG)

Department of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.

Aaron Nagiel (A)

Department of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
Department of Ophthalmology, Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

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Classifications MeSH