ArticlePloS one2014
Modifier genes as therapeutics: the nuclear hormone receptor Rev Erb alpha (Nr1d1) rescues Nr2e3 associated retinal disease.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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.
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.
Who cites it
34 citing papers in PubMed, 42 citations in OpenAlex.
- Enhanced S-cone syndrome in a family: first long-term (12-year) follow-up and literature review.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- Oxidative Stress Signaling and Regenerative Responses in a Larval Zebrafish Model of Retinal Light Damage.Antioxidants (Basel, Switzerland) · 2026Article
- Modifier variants in metabolic pathways are associated with an increased penetrance of Leber's Hereditary Optic Neuropathy.European journal of human genetics : EJHG · 2026Article
- Gene and Stem Cell-Based Therapies for Retinal Degenerative Diseases: Update, Challenges, and Future Directions.Stem cell reviews and reports · 2025Review
- Preclinical biodistribution and toxicology assessment of an AAV5-based subretinal modifier gene therapy for retinitis pigmentosa.Frontiers in medicine · 2025Article
- Retinoic acid related orphan receptor α is a genetic modifier that rescues retinal degeneration in a mouse model of Stargardt disease and Dry AMD.Gene therapy · 2024Article
- Preclinical dose response study shows NR2E3 can attenuate retinal degeneration in the retinitis pigmentosa mouse model RhoGene therapy · 2024Article
- Oxidative stress in retinal pigment epithelium degeneration: from pathogenesis to therapeutic targets in dry age-related macular degeneration.Neural regeneration research · 2023Review
- Identification of potential biomarkers of myopia based on machine learning algorithms.BMC ophthalmology · 2023Article
- Nuclear Receptor Subfamily 2 Group E Member 3 (NR2E3): Role in Retinal Development and Disease.Genes · 2023Review
- Gene Therapy for Retinal Degenerative Diseases: Progress, Challenges, and Future Directions.Investigative ophthalmology & visual science · 2023Review
- Potential therapeutic targets for age-related macular degeneration: The nuclear option.Progress in retinal and eye research · 2023Review
- Modeling Retinitis Pigmentosa with Patient-Derived iPSCs.Advances in experimental medicine and biology · 2023Review
- Gene-agnostic approaches to treating inherited retinal degenerations.Frontiers in cell and developmental biology · 2023Review
- Article
- Common polymorphic OTC variants can act as genetic modifiers of enzymatic activity.Human mutation · 2021Article
- Nr2e3 is a genetic modifier that rescues retinal degeneration and promotes homeostasis in multiple models of retinitis pigmentosa.Gene therapy · 2021Article
- Enhanced S-Cone Syndrome: Spectrum of Clinical, Imaging, Electrophysiologic, and Genetic Findings in a Retrospective Case Series of 56 Patients.Ophthalmology. Retina · 2021Article
- Interspecies Correlations between Human and MouseJournal of clinical medicine · 2021Article
- Novel Pathogenic Sequence Variants inGenes · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
Nuclear hormone receptors play a major role in many important biological processes. Most nuclear hormone receptors are ubiquitously expressed and regulate processes such as metabolism, circadian function, and development. They function in these processes to maintain homeostasis through modulation of transcriptional gene networks. In this study we evaluate the effectiveness of a nuclear hormone receptor gene to modulate retinal degeneration and restore the integrity of the retina. Currently, there are no effective treatment options for retinal degenerative diseases leading to progressive and irreversible blindness. In this study we demonstrate that the nuclear hormone receptor gene Nr1d1 (Rev-Erbα) rescues Nr2e3-associated retinal degeneration in the rd7 mouse, which lacks a functional Nr2e3 gene. Mutations in human NR2E3 are associated with several retinal degenerations including enhanced S cone syndrome and retinitis pigmentosa. The rd7 mouse, lacking Nr2e3, exhibits an increase in S cones and slow, progressive retinal degeneration. A traditional genetic mapping approach previously identified candidate modifier loci. Here, we demonstrate that in vivo delivery of the candidate modifier gene, Nr1d1 rescues Nr2e3 associated retinal degeneration. We observed clinical, histological, functional, and molecular restoration of the rd7 retina. Furthermore, we demonstrate that the mechanism of rescue at the molecular and functional level is through the re-regulation of key genes within the Nr2e3-directed transcriptional network. Together, these findings reveal the potency of nuclear receptors as modulators of disease and specifically of NR1D1 as a novel therapeutic for retinal degenerations.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.