Evidence map›Paper›PMID 35298655›Full record

ArticleStem cells translational medicine2022

Human Retinal Organoids Provide a Suitable Tool for Toxicological Investigations: A Comprehensive Validation Using Drugs and Compounds Affecting the Retina.

Birthe Dorgau, Maria Georgiou, Alexander Chaudhary, Marina Moya-Molina, Joseph Collin, Rachel Queen, Gerrit Hilgen, Tracey Davey, Philip Hewitt, Michael Schmitt and 6 more

Open access · goldAbstract read
In one paragraph

Article in Stem cells translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
4.0field-weighted citation impact, top 5% of its field
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

34 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
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  7. Article
  8. Review
  9. International journal of molecular sciences · 2025
    Article
  10. Review
  11. Retinal organoids mirror CRISPR-Cas9 gene editing efficiency observedMolecular therapy. Methods & clinical development · 2025
    Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. "ArmedFrontiers in cell and developmental biology · 2025
    Review
  19. Article
  20. 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

16 authors at 5 institutions in 3 countries.

Birthe DorgauNewcastle University, Biosciences Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK.
Maria GeorgiouNewcastle University, Biosciences Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK.
Alexander ChaudharyNewcastle University, Biosciences Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK.
Marina Moya-MolinaNewcastle University, Biosciences Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK.
Joseph CollinNewcastle University, Biosciences Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK.
Rachel QueenNewcastle University, Biosciences Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK.
Gerrit HilgenNewcastle University, Biosciences Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK.
Tracey DaveyNewcastle University, Biosciences Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK.
Philip HewittMerck Healthcare KGaA, Darmstadt, Germany.
Michael SchmittMerck Healthcare KGaA, Darmstadt, Germany.
Stefan KustermannPharmaceutical Sciences, F. Hoffmann-La Roche, Pharma Research and Early Development, Roche Innovation Center Basel, Switzerland.
Francois PognanNovartis, PreClinical Safety, Basel, Switzerland.
David H SteelNewcastle University, Biosciences Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK.
Evelyne SernagorNewcastle University, Biosciences Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK.
Lyle ArmstrongNewcastle University, Biosciences Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK.
Majlinda LakoNewcastle University, Biosciences Institute, Faculty of Medical Sciences, Newcastle upon Tyne, UK.ORCID 0000-0003-1327-8573
Newcastle University · GBMerck (Germany) · DENorthumbria University · GBNovartis (Switzerland) · CHRoche (Switzerland) · CH

Funding

Medical Research Council MR/T017503/1National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/C016106/1
6 · The paper itself

Abstract

Retinal drug toxicity screening is essential for the development of safe treatment strategies for a large number of diseases. To this end, retinal organoids derived from human pluripotent stem cells (hPSCs) provide a suitable screening platform due to their similarity to the human retina and the ease of generation in large-scale formats. In this study, two hPSC cell lines were differentiated to retinal organoids, which comprised all key retinal cell types in multiple nuclear and synaptic layers. Single-cell RNA-Seq of retinal organoids indicated the maintenance of retinal ganglion cells and development of bipolar cells: both cell types segregated into several subtypes. Ketorolac, digoxin, thioridazine, sildenafil, ethanol, and methanol were selected as key compounds to screen on retinal organoids because of their well-known retinal toxicity profile described in the literature. Exposure of the hPSC-derived retinal organoids to digoxin, thioridazine, and sildenafil resulted in photoreceptor cell death, while digoxin and thioridazine additionally affected all other cell types, including Müller glia cells. All drug treatments caused activation of astrocytes, indicated by dendrites sprouting into neuroepithelium. The ability to respond to light was preserved in organoids although the number of responsive retinal ganglion cells decreased after drug exposure. These data indicate similar drug effects in organoids to those reported in in vivo models and/or in humans, thus providing the first robust experimental evidence of their suitability for toxicological studies.

Indexed as

Induced Pluripotent Stem CellsOrganoidsCell DifferentiationDigoxinHumansRetinaSildenafil CitrateThioridazineDigoxinSildenafil CitrateThioridazinedrug screeninghuman embryonic stem cellshuman induced pluripotent stem cellsretinaretinal organoidstoxicology

Identifiers

PMID35298655
PMCPMC8929478
OpenAlexW4206174278

What OpenQuestion holds

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LicenceCC BY
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.