ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Corneal fibrosis abrogation by a localized AAV-mediated inhibitor of differentiation 3 (Id3) gene therapy in rabbit eyes in vivo.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. 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 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- A Viscous DES-AAV-Foxo1 Delivery System With High Transfection Efficiency for the Treatment of Corneal Endothelial Dysfunction by Restoring Mitochondria-ER Contacts.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tannic Acid Achieves Rapid Scar-Free Corneal Healing by Chelating Excess Copper to Suppress Aberrant LOX-Mediated Fibrosis.Investigative ophthalmology & visual science · 2026Article
- Alterations in Mitochondrial DNA in Corneal Fibroblast and Myofibroblast Post Injury.Investigative ophthalmology & visual science · 2026Article
- Long-Term Tolerability and Safety of AAV5-Id3 Gene Therapy to Eyes.Translational vision science & technology · 2026Article
- A prevalent disease-associated SNP in the humanNAR molecular medicine · 2026Article
- Mustard Gas Induced Corneal Injury Involves Ferroptosis and p38 MAPK Signaling.Investigative ophthalmology & visual science · 2025Article
- Role of epigenetics in corneal health and disease.Progress in retinal and eye research · 2025Review
- Regenerative Therapy for Corneal Scarring Disorders.Biomedicines · 2024Review
- Mechanical stiffness promotes skin fibrosis via Piezo1-Wnt2/Wnt11-CCL24 positive feedback loop.Cell death & disease · 2024Article
- Analysis of Smad3 in the modulation of stromal extracellular matrix proteins in corneal scarring after alkali injury.Molecular vision · 2024Article
- Sustained and Efficient Delivery of Antivascular Endothelial Growth Factor by the Adeno-associated Virus for the Treatment of Corneal Neovascularization: An Outlook for Its Clinical Translation.Journal of ophthalmology · 2024Review
- Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Previously we found that inhibitor of differentiation 3 (Id3) gene, a transcriptional repressor, efficiently inhibits corneal keratocyte differentiation to myofibroblasts in vitro. This study evaluated the potential of adeno-associated virus 5 (AAV5)-mediated Id3 gene therapy to treat corneal scarring using an established rabbit in vivo disease model. Corneal scarring/fibrosis in rabbit eyes was induced by alkali trauma, and 24 h thereafter corneas were administered with either balanced salt solution AAV5-naked vector, or AAV5-Id3 vector (n = 6/group) via an optimized reported method. Therapeutic effects of AAV5-Id3 gene therapy on corneal pathology and ocular health were evaluated with clinical, histological, and molecular techniques. Localized AAV5-Id3 gene therapy significantly inhibited corneal fibrosis/haze clinically from 2.7 to 0.7 on the Fantes scale in live animals (AAV5-naked versus AAV5-Id3; p < 0.001). Furthermore, AAV5-Id3 treatment significantly reduced profibrotic gene mRNA levels: α-smooth muscle actin (α-SMA) (2.8-fold; p < 0.001), fibronectin (3.2-fold; p < 0.001), collagen I (0.8-fold; p < 0.001), and collagen III (1.4-fold; p < 0.001), as well as protein levels of α-SMA (23.8%; p < 0.001) and collagens (1.8-fold; p < 0.001). The anti-fibrotic activity of AAV5-Id3 is attributed to reduced myofibroblast formation by disrupting the binding of E-box proteins to the promoter of α-SMA, a transforming growth factor-β signaling downstream target gene. In conclusion, these results indicate that localized AAV5-Id3 delivery in stroma caused no clinically relevant ocular symptoms or corneal cellular toxicity in the rabbit eyes.
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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.