Evidence map›Paper›PMID 41655020›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026

AAV NRF2 gene therapy preserves retinal structure and function in rodent models of oxidative damage.

Apolonia Gardner, Shuai Wang, Adam Daniels, Dan Li, Christine Wu, Lucas Lin, Christin Hong, Sophia R Zhao, Richard T Born, Kamil Kruczek and 8 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Apolonia GardnerDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Program in Virology, Harvard Medical School, Boston, MA 02115, USA.
Shuai WangDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Adam DanielsDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Dan LiDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Christine WuDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Lucas LinDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Christin HongDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Sophia R ZhaoDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Richard T BornDepartment of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Kamil KruczekGene Therapy Research, Spark Therapeutics, Philadelphia, PA 19104, USA.
Genevieve WeistGene Therapy Research, Spark Therapeutics, Philadelphia, PA 19104, USA.
Laura Barrio RealGene Therapy Research, Spark Therapeutics, Philadelphia, PA 19104, USA.
Joan WicksGene Therapy Research, Spark Therapeutics, Philadelphia, PA 19104, USA.
Mohamad NayalGene Therapy Research, Spark Therapeutics, Philadelphia, PA 19104, USA.
Ashley CarterGene Therapy Research, Spark Therapeutics, Philadelphia, PA 19104, USA.
Christine OttGene Therapy Research, Spark Therapeutics, Philadelphia, PA 19104, USA.
Virginia HaurigotGene Therapy Research, Spark Therapeutics, Philadelphia, PA 19104, USA.
Constance L CepkoDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: cepko@genetics.med.harvard.edu.

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

Dry age-related macular degeneration is the most frequent cause of visual impairment in individuals over age 50 in developed countries. It is characterized by deposits of oxidized proteins and lipids and results in progressive loss of high-acuity vision. One major risk factor is smoking, which causes oxidative stress in many tissues, including the eye. We previously showed that an adeno-associated viral vector expressing human NRF2 (AAV8/Best1-NRF2), a transcription factor that regulates responses to oxidative damage, slowed degeneration in mouse models of another blinding disorder, retinitis pigmentosa, which also includes oxidative stress. Here, our AAV8/Best1-NRF2 vector was tested in a model of oxidative stress wherein sodium iodate was injected systemically, as this is often used to model dry age-related macular degeneration. Sodium iodate causes acute oxidative damage to the retinal pigment epithelial cells, which provide support to the photoreceptor cells. In addition, this toxin ultimately leads to photoreceptor death. Subretinal injection of AAV8/Best1-NRF2 led to protection of the retinal pigment epithelium and photoreceptors, as well as preservation of visual function, in rat and mouse sodium iodate models. AAV8/Best1-NRF2 may serve as an effective gene-agnostic therapy for diseases with oxidative stress, including dry age-related macular degeneration.

Indexed as

Genetic TherapyGenetic VectorsMacular DegenerationNF-E2-Related Factor 2Oxidative StressRetinaAnimalsDependovirusDisease Models, AnimalGene Therapy AgentsHumansIodatesMiceRatsRetinal Pigment EpitheliumIodatesNF-E2-Related Factor 2sodium iodateadeno-associated virusdry AMDgene therapymouse modelNRF2oxidative stressrat modelretinal pigment epitheliumsodium iodate modelsubretinal injection

Identifiers

PMID41655020
PMCPMC13238944

What OpenQuestion 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 OpenQuestion graph.