ArticlePloS one2013
BMP7 gene transfer via gold nanoparticles into stroma inhibits corneal fibrosis in vivo.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 119 citations in OpenAlex.
- Advancing Treatment of Degenerative Eye Diseases at the Nanoscale.Smart medicine · 2026Review
- Myogenic Differentiation (MyoD) Gene Expression in Cornea and Role in Corneal Myofibroblast Dedifferentiation.Investigative ophthalmology & visual science · 2026Article
- Long-Term Tolerability and Safety of AAV5-Id3 Gene Therapy to Eyes.Translational vision science & technology · 2026Article
- Advances in the management of ocular anterior segment diseases using biomaterials-based drug delivery systems.Journal of biomaterials applications · 2026Review
- Article
- Genetic Basis of Non-Syndromic Childhood Glaucoma Associated with Anterior Segment Dysgenesis: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Bone morphogenetic proteins (BMPs) at the forefront of ocular diseases and therapeutics.Eye and vision (London, England) · 2025Review
- Localization of fluorescent gold nanoparticles throughout the eye after topical administration.Frontiers in medicine · 2025Article
- Article
- Nano-Based Drug Approaches to Proliferative Vitreoretinopathy Instead of Standard Vitreoretinal Surgery.International journal of molecular sciences · 2024Review
- Regenerative Therapy for Corneal Scarring Disorders.Biomedicines · 2024Review
- Review
- Analysis of Smad3 in the modulation of stromal extracellular matrix proteins in corneal scarring after alkali injury.Molecular vision · 2024Article
- NBL1 Reduces Corneal Fibrosis and Scar Formation after Wounding.Biomolecules · 2023Article
- [Gene therapy in ophthalmology].Die Ophthalmologie · 2023Review
- Next-Generation Nanomedicine Approaches for the Management of Retinal Diseases.Pharmaceutics · 2023Review
- Corneal gene therapy: Structural and mechanistic understanding.The ocular surface · 2023Article
- Review
- Corneal stromal repair and regeneration.Progress in retinal and eye research · 2022Review
- Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
This study examined the effects of BMP7 gene transfer on corneal wound healing and fibrosis inhibition in vivo using a rabbit model. Corneal haze in rabbits was produced with the excimer laser performing -9 diopters photorefractive keratectomy. BMP7 gene was introduced into rabbit keratocytes by polyethylimine-conjugated gold nanoparticles (PEI2-GNPs) transfection solution single 5-minute topical application on the eye. Corneal haze and ocular health in live animals was gauged with stereo- and slit-lamp biomicroscopy. The levels of fibrosis [α-smooth muscle actin (αSMA), F-actin and fibronectin], immune reaction (CD11b and F4/80), keratocyte apoptosis (TUNEL), calcification (alizarin red, vonKossa and osteocalcin), and delivered-BMP7 gene expression in corneal tissues were quantified with immunofluorescence, western blotting and/or real-time PCR. Human corneal fibroblasts (HCF) and in vitro experiments were used to characterize the molecular mechanism mediating BMP7's anti-fibrosis effects. PEI2-GNPs showed substantial BMP7 gene delivery into rabbit keratocytes in vivo (2×10(4) gene copies/ug DNA). Localized BMP7 gene therapy showed a significant corneal haze decrease (1.68±0.31 compared to 3.2±0.43 in control corneas; p<0.05) in Fantes grading scale. Immunostaining and immunoblot analyses detected significantly reduced levels of αSMA (46±5% p<0.001) and fibronectin proteins (48±5% p<0.01). TUNEL, CD11b, and F4/80 assays revealed that BMP7 gene therapy is nonimmunogenic and nontoxic for the cornea. Furthermore, alizarin red, vonKossa and osteocalcin analyses revealed that localized PEI2-GNP-mediated BMP7 gene transfer in rabbit cornea does not cause calcification or osteoblast recruitment. Immunofluorescence of BMP7-transefected HCFs showed significantly increased pSmad-1/5/8 nuclear localization (>88%; p<0.0001), and immunoblotting of BMP7-transefected HCFs grown in the presence of TGFβ demonstrated significantly enhanced pSmad-1/5/8 (95%; p<0.001) and Smad6 (53%, p<0.001), and decreased αSMA (78%; p<0.001) protein levels. These results suggest that localized BMP7 gene delivery in rabbit cornea modulates wound healing and inhibits fibrosis in vivo by counter balancing TGFβ1-mediated profibrotic Smad signaling.
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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.