ArticleThe Journal of clinical investigation2014
Postnatal manipulation of Pax6 dosage reverses congenital tissue malformation defects.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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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.
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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.
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Who cites it
62 citing papers in PubMed.
- Ataluren treatment of patients with nonsense mutation dystrophinopathy.Muscle & nerve · 2014Trial
- Characterization of a spontaneous microphthalmia-like mutant mouse with isolated ocular defects.PloS one · 2026Article
- A novel minimally humanized mouse model of aniridia for preclinical evaluation of CRISPR gene editing strategies.Frontiers in genome editing · 2026Article
- AAV-delivered engineered suppressor tRNA rescues visual function in mice with an inherited retinal disease.Nature communications · 2025Article
- Analysis of mouse lens morphological and proteomic abnormalities following deletion of the βB3-crystallin promoter.Experimental eye research · 2025Article
- Genetic Basis of Non-Syndromic Childhood Glaucoma Associated with Anterior Segment Dysgenesis: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Molecular insights into foveal hypoplasia: development, genetics, mechanisms, and models.Molecular vision · 2025Review
- A human-like model of aniridia-associated keratopathy for mechanistic and therapeutic studies.JCI insight · 2024Article
- Genetic analysis using next-generation sequencing and multiplex ligation probe amplification in Chinese aniridia patients.Orphanet journal of rare diseases · 2024Article
- Characterization of neural damage and neuroinflammation in Pax6 small-eye mice.Experimental eye research · 2024Article
- Restoration of functional PAX6 in aniridia patient iPSC-derived ocular tissue models using repurposed nonsense suppression drugs.Molecular therapy. Nucleic acids · 2023Article
- ABE8e Corrects Pax6-Aniridic Variant in Humanized Mouse ESCs and via LNPs in Ex Vivo Cortical Neurons.Ophthalmology and therapy · 2023Article
- Congenital aniridia beyond black eyes: From phenotype and novel genetic mechanisms to innovative therapeutic approaches.Progress in retinal and eye research · 2023Review
- Gene therapies in pediatric ophthalmology.Frontiers in ophthalmology · 2023Review
- Review
- Functional restoration of mouse Nf1 nonsense alleles in differentiated cultured neurons.Journal of human genetics · 2022Article
- Translational enhancement by base editing of the Kozak sequence rescues haploinsufficiency.Nucleic acids research · 2022Article
- Investigation of PTC124-mediated translational readthrough in a retinal organoid model of AIPL1-associated Leber congenital amaurosis.Stem cell reports · 2022Article
- Ataluren binds to multiple protein synthesis apparatus sites and competitively inhibits release factor-dependent termination.Nature communications · 2022Article
- Long-term retinal protection by MEK inhibition in Pax6 haploinsufficiency mice.Experimental eye research · 2022Article
2 more citing papers are in PubMed but not listed here.
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6 authors.
Funding
Abstract
Aniridia is a congenital and progressive panocular condition with poor visual prognosis that is associated with brain, olfactory, and pancreatic abnormalities. Development of aniridia is linked with nonsense mutations that result in paired box 6 (PAX6) haploinsufficiency. Here, we used a mouse model of aniridia to test the hypothesis that manipulation of Pax6 dosage through a mutation-independent nonsense mutation suppression strategy would limit progressive, postnatal damage in the eye. We focused on the nonsense suppression drugs 3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid (ataluren) and gentamicin. Remarkably, we demonstrated that nonsense suppression not only inhibited disease progression but also stably reversed corneal, lens, and retinal malformation defects and restored electrical and behavioral responses of the retina. The most successful results were achieved through topical application of the drug formulation START (0.9% sodium chloride, 1% Tween 80, 1% powdered ataluren, 1% carboxymethylcellulose), which was designed to enhance particle dispersion and to increase suspension viscosity. These observations suggest that the eye retains marked developmental plasticity into the postnatal period and remains sensitive to molecular remodeling. Furthermore, these data indicate that other neurological developmental anomalies associated with dosage-sensitive genetic mutations may be reversible through nonsense suppression therapeutics.
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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.