Evidence map›Paper›PMID 36084639›Full record

ArticleStem cell reports2022

Investigation of PTC124-mediated translational readthrough in a retinal organoid model of AIPL1-associated Leber congenital amaurosis.

Amy Leung, Almudena Sacristan-Reviriego, Pedro R L Perdigão, Hali Sai, Michalis Georgiou, Angelos Kalitzeos, Amanda-Jayne F Carr, Peter J Coffey, Michel Michaelides, James Bainbridge and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 12% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Restoring Sight: The Journey of AIPL1 from Discovery to Therapy.International journal of molecular sciences · 2025
    Review
  6. Article
  7. Retinal Organoids: Innovative Tools for Understanding Retinal Degeneration.International journal of molecular sciences · 2025
    Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. HGG advances · 2023
    Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
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

12 authors at 1 institution in 1 country.

Amy LeungUCL Institute of Ophthalmology, London EC1V 9EL, UK.
Almudena Sacristan-ReviriegoUCL Institute of Ophthalmology, London EC1V 9EL, UK.
Pedro R L PerdigãoUCL Institute of Ophthalmology, London EC1V 9EL, UK.
Hali SaiUCL Institute of Ophthalmology, London EC1V 9EL, UK.
Michalis GeorgiouUCL Institute of Ophthalmology, London EC1V 9EL, UK; Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK.
Angelos KalitzeosUCL Institute of Ophthalmology, London EC1V 9EL, UK; Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK.
Amanda-Jayne F CarrUCL Institute of Ophthalmology, London EC1V 9EL, UK.
Peter J CoffeyUCL Institute of Ophthalmology, London EC1V 9EL, UK.
Michel MichaelidesUCL Institute of Ophthalmology, London EC1V 9EL, UK; Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK.
James BainbridgeUCL Institute of Ophthalmology, London EC1V 9EL, UK; Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK.
Michael E CheethamUCL Institute of Ophthalmology, London EC1V 9EL, UK.
Jacqueline van der SpuyUCL Institute of Ophthalmology, London EC1V 9EL, UK. Electronic address: j.spuy@ucl.ac.uk.
University College London · GB

Funding

Medical Research Council MR/P02582X/1
6 · The paper itself

Abstract

Leber congenital amaurosis type 4 (LCA4), caused by AIPL1 mutations, is characterized by severe sight impairment in infancy and rapidly progressing degeneration of photoreceptor cells. We generated retinal organoids using induced pluripotent stem cells (iPSCs) from renal epithelial cells obtained from four children with AIPL1 nonsense mutations. iPSC-derived photoreceptors exhibited the molecular hallmarks of LCA4, including undetectable AIPL1 and rod cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE6) compared with control or CRISPR-corrected organoids. Increased levels of cGMP were detected. The translational readthrough-inducing drug (TRID) PTC124 was investigated as a potential therapeutic agent. LCA4 retinal organoids exhibited low levels of rescue of full-length AIPL1. However, this was insufficient to fully restore PDE6 in photoreceptors and reduce cGMP. LCA4 retinal organoids are a valuable platform for in vitro investigation of novel therapeutic agents.

Indexed as

Leber Congenital AmaurosisAdaptor Proteins, Signal TransducingCarrier ProteinsChildCodon, NonsenseEye ProteinsGuanosine MonophosphateHumansOrganoidsOxadiazolesPhosphoric Diester HydrolasesAdaptor Proteins, Signal TransducingAIPL1 protein, humanatalurenCarrier ProteinsCodon, NonsenseEye ProteinsGuanosine MonophosphateOxadiazolesPhosphoric Diester HydrolasesCRISPR-Cas9gene editinginduced pluripotent stem cellsinherited retinal degenerationLCALeber congenital amaurosisrenal epithelial cell reprogrammingretinal organoidsROstranslation readthrough-inducing drugTRID

Identifiers

PMID36084639
PMCPMC9561542
OpenAlexW4297244126

What Socratic holds

Textmetadata
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 Socratic graph.