Evidence map›Paper›PMID 33491671›Full record

ArticleJCI insight2021

Nrf2 overexpression rescues the RPE in mouse models of retinitis pigmentosa.

David M Wu, Xuke Ji, Maryna V Ivanchenko, Michelle Chung, Mary Piper, Parimal Rana, Sean K Wang, Yunlu Xue, Emma West, Sophia R Zhao and 4 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing 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

45 citing papers in PubMed, 68 citations in OpenAlex.

  1. Trial
  2. Article
  3. AAV-NRF2 protects retinal and choroidal vasculature in a GDF15-dependent manner in an oxidative damage model of AMD.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. AAV NRF2 gene therapy preserves retinal structure and function in rodent models of oxidative damage.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  6. Article
  7. Article
  8. Selective deletion ofiScience · 2026
    Article
  9. Article
  10. Article
  11. Review
  12. RPE-specific MCT2 expression promotes cone survival in models of retinitis pigmentosa.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Retinal Penetrating Adeno-Associated Virus.Investigative ophthalmology & visual science · 2024
    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 4 institutions in 2 countries.

David M WuMassachusetts Eye and Ear Infirmary Retina Service, Department of Ophthalmology.
Xuke JiMassachusetts Eye and Ear Infirmary Retina Service, Department of Ophthalmology.
Maryna V IvanchenkoDepartment of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
Michelle ChungDepartments of Genetics and Ophthalmology, Blavatnik Institute, and.
Mary PiperDepartment of Bioinformatics, T.H. Chan Harvard School of Public Health, Boston, Massachusetts, USA.
Parimal RanaDepartments of Genetics and Ophthalmology, Blavatnik Institute, and.
Sean K WangDepartments of Genetics and Ophthalmology, Blavatnik Institute, and.
Yunlu XueDepartments of Genetics and Ophthalmology, Blavatnik Institute, and.
Emma WestDepartments of Genetics and Ophthalmology, Blavatnik Institute, and.
Sophia R ZhaoDepartments of Genetics and Ophthalmology, Blavatnik Institute, and.
Hongbin XuDepartments of Genetics and Ophthalmology, Blavatnik Institute, and.
Marcelo CicconetImage and Data Analysis Core, Harvard Medical School, Boston, Massachusetts, USA.
Wenjun XiongDepartment of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
Constance L CepkoDepartment of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
Harvard University · USHoward Hughes Medical Institute · USMassachusetts Eye and Ear Infirmary · USCity University of Hong Kong · HK

Funding

Gene Therapy for Hearing and Balance DisordersR01DC016932 · NIDCD · HARVARD MEDICAL SCHOOL · PI DAVID P COREY, Benjamin Peter Kleinstiver · 2018 to 2026
$2.8M
Molecular Profiling of Rods to Identify New Therapies for Retinal DegenerationsK08EY023993 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI WU, DAVID · 2014 to 2018
$1.1M
Investigation of the Mechanisms of Cone Degeneration in Retinitis PigmentosaK99EY030951 · NEI · HARVARD MEDICAL SCHOOL · PI XUE, YUNLU · 2020 to 2022
$242k
Howard Hughes Medical InstituteNEI NIH HHS K08 EY023993NEI NIH HHS K99 EY030951NIDCD NIH HHS R01 DC016932
6 · The paper itself

Abstract

Nrf2, a transcription factor that regulates the response to oxidative stress, has been shown to rescue cone photoreceptors and slow vision loss in mouse models of retinal degeneration (rd). The retinal pigment epithelium (RPE) is damaged in these models, but whether it also could be rescued by Nrf2 has not been previously examined. We used an adeno-associated virus (AAV) with an RPE-specific (Best1) promoter to overexpress Nrf2 in the RPE of rd mice. Control rd mice showed disruption of the regular array of the RPE, as well as loss of RPE cells. Cones were lost in circumscribed regions within the cone photoreceptor layer. Overexpression of Nrf2 specifically in the RPE was sufficient to rescue the RPE, as well as the disruptions in the cone photoreceptor layer. Electron microscopy showed compromised apical microvilli in control rd mice but showed preserved microvilli in Best1-Nrf2-treated mice. The rd mice treated with Best1-Nrf2 had slightly better visual acuity. Transcriptome profiling showed that Nrf2 upregulates multiple oxidative defense pathways, reversing declines seen in the glutathione pathway in control rd mice. In summary, Nrf2 overexpression in the RPE preserves RPE morphology and survival in rd mice, and it is a potential therapeutic for diseases involving RPE degeneration, including age-related macular degeneration (AMD).

Indexed as

AnimalsDisease Models, AnimalHumansMacular DegenerationMiceMice, Mutant StrainsMice, TransgenicMicroscopy, Electron, ScanningNF-E2-Related Factor 2Recombinant ProteinsRetinal Cone Photoreceptor CellsRetinal DegenerationRetinal Pigment EpitheliumRetinitis PigmentosaUp-RegulationVisual AcuityNFE2L2 protein, humanNF-E2-Related Factor 2Recombinant ProteinsGene therapyOphthalmology

Identifiers

PMID33491671
PMCPMC7934854
OpenAlexW3122891282

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.