Evidence map›Paper›PMID 35042858›Full record

ArticleNature communications2022

Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration.

Jen-Zen Chuang, Nan Yang, Nobuyuki Nakajima, Wataru Otsu, Cheng Fu, Howard Hua Yang, Maxwell Ping Lee, Armaan Fazal Akbar, Tudor Constantin Badea, Ziqi Guo and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
8.0field-weighted citation impact, top 1% 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

30 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Review of the clinical electrooculogram - Part 1: Mechanism of the Light-Rise.Documenta ophthalmologica. Advances in ophthalmology · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Duplication of a conserved mitochondrial enzyme gene arms parasitoid wasps with venom cytotoxicity and oogenesis regulation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Article
  8. Review
  9. Review
  10. Clic6 Deficiency Triggers Aberrant Apical Microvilli in RPE.Investigative ophthalmology & visual science · 2025
    Article
  11. Article
  12. Review
  13. A zebrafish model ofFrontiers in cell and developmental biology · 2025
    Article
  14. Review
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. 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

14 authors at 7 institutions in 3 countries.

Jen-Zen Chuang *Department of Ophthalmology, Margaret M. Dyson Vision Research Institute, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA. jzchuang@med.cornell.edu.ORCID http://orcid.org/0000-0001-7056-8871
Nan Yang *Department of Ophthalmology, Margaret M. Dyson Vision Research Institute, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.
Nobuyuki Nakajima *Department of Ophthalmology, Margaret M. Dyson Vision Research Institute, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.
Wataru Otsu *Department of Ophthalmology, Margaret M. Dyson Vision Research Institute, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0002-5930-1954
Cheng FuDepartment of Ophthalmology, Margaret M. Dyson Vision Research Institute, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.
Howard Hua YangThe Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Maxwell Ping LeeThe Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-3738-1292
Armaan Fazal AkbarNational Eye Institute, National institute of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-4255-9019
Tudor Constantin BadeaNational Eye Institute, National institute of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-3086-6713
Ziqi GuoDepartment of Ophthalmology, Margaret M. Dyson Vision Research Institute, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.
Afnan NuruzzamanDepartment of Ophthalmology, Margaret M. Dyson Vision Research Institute, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.ORCID http://orcid.org/0000-0003-1819-9946
Kuo-Shun HsuDepartment of Ophthalmology, Margaret M. Dyson Vision Research Institute, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.
Joshua L DunaiefFM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ching-Hwa SungDepartment of Ophthalmology, Margaret M. Dyson Vision Research Institute, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA. chsung@med.cornell.edu.ORCID http://orcid.org/0000-0002-3468-5867
Cornell University · USNational Institutes of Health · USGifu Pharmaceutical University · JPNational Eye Institute · USPenn Presbyterian Medical Center · USTokai University · JPTransylvania University of Brașov · RO

Funding

Scientific TransparencyP30EY001583 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CLAIRE H MITCHELL · 1985 to 2026
$19.5M
TRD #3: An automated and streamlined pipeline for in-situ molecular microscopyP41GM103310 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI DE MARCO, ALEX, KIEFT, JEFFREY S · 2012 to 2021
$14.7M
Integrated analyses of genetics, epigenetics, and gene expressionZIHBC011703 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LEE, MAXWELL · 2016 to 2025
$10.9M
Retinal Iron Transport in Health and DiseaseR01EY015240 · NEI · UNIVERSITY OF PENNSYLVANIA · PI JOSHUA L DUNAIEF · 2004 to 2026
$10.4M
Endosome regulated retinal homeostasis and diseaseR01EY029428 · NEI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHING-HWA SUNG · 2018 to 2026
$3.8M
The IL-6 Induced Retinal Iron Sequestration ResponseR01EY028916 · NEI · UNIVERSITY OF PENNSYLVANIA · PI DUNAIEF, JOSHUA L · 2019 to 2023
$2.4M
Modeling and mechanistic investigation of a novel dry AMD mouse model with CLIC4 deleted in RPER01EY032966 · NEI · WEILL MEDICAL COLL OF CORNELL UNIV · PI SUNG, CHING-HWA · 2021 to 2024
$1.7M
NEI NIH HHS P30 EY001583NEI NIH HHS R01 EY015240NEI NIH HHS R01 EY028916NEI NIH HHS R01 EY029428NEI NIH HHS R01 EY032966NIGMS NIH HHS P41 GM103310
6 · The paper itself

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly. Dry AMD has unclear etiology and no treatment. Lipid-rich drusen are the hallmark of dry AMD. An AMD mouse model and insights into drusenogenesis are keys to better understanding of this disease. Chloride intracellular channel 4 (CLIC4) is a pleomorphic protein regulating diverse biological functions. Here we show that retinal pigment epithelium (RPE)-specific Clic4 knockout mice exhibit a full spectrum of functional and pathological hallmarks of dry AMD. Multidisciplinary longitudinal studies of disease progression in these mice support a mechanistic model that links RPE cell-autonomous aberrant lipid metabolism and transport to drusen formation.

Indexed as

AnimalsCell DeathChloride ChannelsDisease Models, AnimalFundus OculiHomeostasisLipid MetabolismMacular DegenerationMiceMice, Inbred C57BLMice, KnockoutMitochondrial ProteinsMutationOrgan SpecificityRetinal DrusenRetinal Pigment EpitheliumChloride ChannelsCLIC protein, mouseMitochondrial Proteins

Identifiers

PMID35042858
PMCPMC8766482
OpenAlexW4206582208

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.