Evidence map›Paper›PMID 36084637›Full record

ArticleStem cell reports2022

In vitro modeling and rescue of ciliopathy associated with IQCB1/NPHP5 mutations using patient-derived cells.

Kamil Kruczek, Zepeng Qu, Emily Welby, Hiroko Shimada, Suja Hiriyanna, Milton A English, Wadih M Zein, Brian P Brooks, Anand Swaroop

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 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% 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

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

  1. Pooled it
  2. International journal of molecular sciences · 2025
    Article
  3. Article
  4. Review
  5. Review
  6. Retinal Organoids: Innovative Tools for Understanding Retinal Degeneration.International journal of molecular sciences · 2025
    Review
  7. Article
  8. Review
  9. The role ofTranslational cancer research · 2024
    Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Clinical and Molecular Aspects of C2orf71/PCARE in Retinal Diseases.International journal of molecular sciences · 2023
    Review
  17. Article
  18. Eupatilin improves cilia defects in human CEP290 ciliopathy models.bioRxiv : the preprint server for biology · 2023
    Article
  19. 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

9 authors at 2 institutions in 1 country.

Kamil KruczekNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.
Zepeng QuNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.
Emily WelbyNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.
Hiroko ShimadaNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.
Suja HiriyannaOcular Gene Therapy Core, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Milton A EnglishNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA.
Wadih M ZeinOphthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Brian P BrooksOphthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Anand SwaroopNeurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD 20892, USA. Electronic address: swaroopa@nei.nih.gov.
National Eye Institute · USNational Institutes of Health · US

Funding

Regulation of retinal developmentZIAEY000450 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2009 to 2025
$71.0M
Mechanisms, modeling and therapies of retinal and macular neurodegenerationZIAEY000546 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2015 to 2025
$36.3M
Intramural NIH HHS ZIA EY000450Intramural NIH HHS ZIA EY000546
6 · The paper itself

Abstract

Mutations in the IQ calmodulin-binding motif containing B1 (IQCB1)/NPHP5 gene encoding the ciliary protein nephrocystin 5 cause early-onset blinding disease Leber congenital amaurosis (LCA), together with kidney dysfunction in Senior-Løken syndrome. For in vitro disease modeling, we obtained dermal fibroblasts from patients with NPHP5-LCA that were reprogrammed into induced pluripotent stem cells (iPSCs) and differentiated into retinal pigment epithelium (RPE) and retinal organoids. Patient fibroblasts and RPE demonstrated aberrantly elongated ciliary axonemes. Organoids revealed impaired development of outer segment structures, which are modified primary cilia, and mislocalization of visual pigments to photoreceptor cell soma. All patient-derived cells showed reduced levels of CEP290 protein, a critical cilia transition zone component interacting with NPHP5, providing a plausible mechanism for aberrant ciliary gating and cargo transport. Disease phenotype in NPHP5-LCA retinal organoids could be rescued by adeno-associated virus (AAV)-mediated IQCB1/NPHP5 gene augmentation therapy. Our studies thus establish a human disease model and a path for treatment of NPHP5-LCA.

Indexed as

CalmodulinCiliopathiesAntigens, NeoplasmCalmodulin-Binding ProteinsCell Cycle ProteinsCytoskeletal ProteinsHumansMutationRetinal PigmentsAntigens, NeoplasmCalmodulinCalmodulin-Binding ProteinsCell Cycle ProteinsCep290 protein, humanCytoskeletal ProteinsIQCB1 protein, humanRetinal Pigmentsgene therapyLeber congenital amaurosispatient-derived iPSCphotoreceptorprimary ciliaretinal organoidsRPESenior-Løken syndromestem cellsvision

Identifiers

PMID36084637
PMCPMC9561628
OpenAlexW4297244162

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.