ArticleInvestigative ophthalmology & visual science2011
Significant inhibition of corneal scarring in vivo with tissue-selective, targeted AAV5 decorin gene therapy.
Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 90 citations in OpenAlex.
- PDGF-Stimulated Corneal Keratocyte Motility and Migration Patterns on Aligned Collagen Fibrils Are Inhibited by Decorin.International journal of molecular sciences · 2026Article
- Myogenic Differentiation (MyoD) Gene Expression in Cornea and Role in Corneal Myofibroblast Dedifferentiation.Investigative ophthalmology & visual science · 2026Article
- Early Transcriptomic Response of Human Iris Stromal Cells During Herpes Simplex Virus Entry Reveals Interplay Between Cell Glycocalyx and Viral Exploitation.International journal of molecular sciences · 2026Article
- Long-Term Tolerability and Safety of AAV5-Id3 Gene Therapy to Eyes.Translational vision science & technology · 2026Article
- Progressive Insights into 3D Bioprinting for Corneal Tissue Restoration.Advanced healthcare materials · 2026Review
- The Role of Decorin in the Ocular Surface: Structure, Function, and Therapeutic Potential.Proteoglycan research · 2025Article
- Effect of Chemical Injury on Autophagy in Canine Corneal Stromal Fibroblasts.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2025Article
- Effect of Decorin and Aligned Collagen Fibril Topography on TGF-β1 Activation of Corneal Keratocytes.Bioengineering (Basel, Switzerland) · 2025Article
- Review
- 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
- Molecular cues for immune cells from small leucine-rich repeat proteoglycans in their extracellular matrix-associated and free forms.Matrix biology : journal of the International Society for Matrix Biology · 2023Review
- Stromal matrix directs corneal fibroblasts to re-express keratocan after injury and transplantation.Disease models & mechanisms · 2023Article
- [Gene therapy in ophthalmology].Die Ophthalmologie · 2023Review
- Small leucine rich proteoglycans: Biology, function and their therapeutic potential in the ocular surface.The ocular surface · 2023Review
- Corneal gene therapy: Structural and mechanistic understanding.The ocular surface · 2023Article
- Review
- Carbofuran pesticide toxicity to the eye.Experimental eye research · 2023Review
- Characterization of C-X-C chemokine receptor type 5 in the cornea and role in the inflammatory response after corneal injury.Experimental eye research · 2023Article
- Corneal injury is associated with stromal and vascular alterations within cranial dura mater.PloS one · 2023Article
- Role of Decorin in the Lens and Ocular Diseases.Cells · 2022Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThis study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the stroma with adeno-associated virus serotype 5 (AAV5) inhibits corneal fibrosis in vivo without significant side effects.
methodsAn in vivo rabbit model of corneal fibrosis was used. Targeted decorin gene therapy was delivered to the rabbit cornea by a single topical application of AAV5 (100 μL; 6.5 × 10(12) μg/mL) onto the bare stroma for 2 minutes. The levels of corneal fibrosis were determined with stereomicroscopy, slit lamp biomicroscopy, α-smooth muscle actin (αSMA), fibronectin, and F-actin immunocytochemistry, and/or immunoblotting. CD11b, F4/80 immunocytochemistry, and TUNEL assay were used to examine immunogenicity and cytotoxicity of AAV5 to the cornea. Transmission electron microscopy (TEM) was used to investigate ultrastructural features. Slot-blot-quantified the copy number of AAV5-delivered decorin genes.
resultsSelective decorin delivery into the stroma showed a significant (P < 0.01) decrease in corneal haze (1.3 ± 0.3) compared with the no-decorin-delivered control rabbit corneas (3 ± 0.4) quantified using slit lamp biomicroscopy. Immunostaining and immunoblot analyses detected significantly reduced levels of αSMA, F-actin, and fibronectin proteins (59%-73%; P < 0.001 or <0.01) in decorin-delivered rabbit corneas compared with the no-decorin-delivered controls. The visual clinical eye examination, slit lamp clinical studies, TUNEL, CD11b, and F4/80 assays revealed that AAV5-mediated decorin gene therapy is nonimmunogenic and nontoxic for the cornea. TEM studies suggested that decorin gene delivery does not jeopardize collagen fibrillogenesis as no significant differences in collagen fibril diameter and arrangement were observed in decorin-delivered and no-decorin-delivered control corneas.
conclusionsTissue-targeted AAV5-mediated decorin gene therapy is effective and safe for treating corneal fibrosis in vivo.
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Registered trials
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