Evidence map›Paper›PMID 34738615›Full record

ArticleDevelopment (Cambridge, England)2021

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

Sumitha Prameela Bharathan, Angela Ferrario, Kayla Stepanian, G Esteban Fernandez, Mark W Reid, Justin S Kim, Chloe Hutchens, Narine Harutyunyan, Carolyn Marks, Matthew E Thornton and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Development (Cambridge, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Article
  2. Article
  3. Animal models for the evaluation of retinal stem cell therapies.Progress in retinal and eye research · 2025
    Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. The Prospects for Retinal Organoids in Treatment of Retinal Diseases.Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Sumitha Prameela BharathanDepartment of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.ORCID 0000-0002-5830-8273
Angela FerrarioDepartment of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
Kayla StepanianDepartment of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
G Esteban FernandezThe Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.ORCID 0000-0002-8393-9229
Mark W ReidDepartment of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
Justin S KimDepartment of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
Chloe HutchensDepartment of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
Narine HarutyunyanDepartment of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
Carolyn MarksCore Center of Excellence in Nano Imaging, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
Matthew E ThorntonMaternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Brendan H GrubbsMaternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
David CobrinikDepartment of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.ORCID 0000-0002-4478-2417
Jennifer G AparicioDepartment of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.ORCID 0000-0002-6442-3032
Aaron NagielDepartment of Surgery, The Vision Center, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.ORCID 0000-0001-7275-6980

Funding

Human Specific Signaling Circuitry in Cone Precursor DevelopmentR01EY026661 · NEI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI COBRINIK, DAVID · 2016 to 2019
$1.7M
Development and Maintenance of the Human Photoreceptor-Bipolar Cell Synapse.K08EY030924 · NEI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI NAGIEL, AARON · 2020 to 2024
$1.1M
NEI NIH HHS K08 EY030924NEI NIH HHS R01 EY026661
6 · The paper itself

Abstract

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.

Indexed as

Cell LineHuman Embryonic Stem CellsHumansInduced Pluripotent Stem CellsOrganoidsRetinaBipolar cellHuman fetal retinaHuman retinal organoidOuter plexiform layerPhotoreceptorRibbon synapse

Identifiers

PMID34738615
PMCPMC8714069

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.