ArticleInvestigative ophthalmology & visual science2010
Development of a gene therapy virus with a glucocorticoid-inducible MMP1 for the treatment of steroid glaucoma.
Article in Investigative ophthalmology & visual science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 55 citations in OpenAlex.
- Gene therapy for glaucoma: Targeting key mechanisms.Vision research · 2024Review
- Development and testing of a metabolic chamber for effluent collection during whole eye perfusions.Experimental eye research · 2023Article
- The Role of Metalloproteinases and Their Tissue Inhibitors on Ocular Diseases: Focusing on Potential Mechanisms.International journal of molecular sciences · 2022Review
- Long-Term Decrease of Intraocular Pressure in Rats by Viral Delivery of miR-146a.Translational vision science & technology · 2021Article
- Normal and glaucomatous outflow regulation.Progress in retinal and eye research · 2021Review
- Cathepsin B Localizes in the Caveolae and Participates in the Proteolytic Cascade in Trabecular Meshwork Cells. Potential New Drug Target for the Treatment of Glaucoma.Journal of clinical medicine · 2020Article
- Novel Drug Delivery Systems Fighting Glaucoma: Formulation Obstacles and Solutions.Pharmaceutics · 2020Review
- C3 Transferase-Expressing scAAV2 Transduces Ocular Anterior Segment Tissues and Lowers Intraocular Pressure in Mouse and Monkey.Molecular therapy. Methods & clinical development · 2020Article
- Glucocorticoid-Induced Ocular Hypertension: Origins and New Approaches to Minimize.Expert review of ophthalmology · 2020Article
- Gene transfer to the outflow tract.Experimental eye research · 2017Review
- Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine.Progress in retinal and eye research · 2017Review
- Aberrant Collagen Composition of the Trabecular Meshwork Results in Reduced Aqueous Humor Drainage and Elevated IOP in MMP-9 Null Mice.Investigative ophthalmology & visual science · 2016Article
- Inducible scAAV2.GRE.MMP1 lowers IOP long-term in a large animal model for steroid-induced glaucoma gene therapy.Gene therapy · 2016Article
- The autophagic lysosomal system in outflow pathway physiology and pathophysiology.Experimental eye research · 2016Review
- Discovery of Molecular Therapeutics for Glaucoma: Challenges, Successes, and Promising Directions.Journal of medicinal chemistry · 2016Review
- Extracellular matrix in the trabecular meshwork: intraocular pressure regulation and dysregulation in glaucoma.Experimental eye research · 2015Review
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- Methods for gene transfer to the central nervous system.Advances in genetics · 2014Review
- Development of a model of elevated intraocular pressure in rats by gene transfer of bone morphogenetic protein 2.Investigative ophthalmology & visual science · 2013Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo design a glucocorticoid-inducible virus vector overexpressing recombinant matrix metalloproteinase 1 (MMP1) and counteract extracellular matrix deposition in the trabecular meshwork only when steroid is present.
methodsEndogenous MMP1 expression was measured in primary human trabecular meshwork cells (HTM) treated with dexamethasone (DEX), triamcinolone acetate, and prednisolone acetate by TaqMan PCR. Wild-type and mutant MMP1 cDNAs were cloned downstream of a glucocorticoid response element (GRE) and P(TAL) promoter. Adenoviruses AdhGRE.MMP1 and AdhGRE.mutMMP1 were generated by homologous recombination. HTM cells and perfused human anterior segments were infected with the viruses, with and without DEX. MMP1 mRNA and protein were analyzed by TaqMan PCR, Western blot analysis, and ELISA. Activity of secreted MMP1 was evaluated by FRET and rat tail collagen type I assays. Immunohistochemistry was performed by double-labeling with anti-human MMP1 and collagen type I antibodies.
resultsEndogenous MMP1 expression was greatly downregulated by the steroids. DEX-treated cells and perfused organ cultures infected with AdhGRE.MMP1 secreted high levels of MMP1. Induction of MMP1 cycled on and off with the addition or removal of DEX. Secreted wild-type MMP1 degraded collagen type I after activation, whereas secreted mutMMP1 did not. Immunohistochemistry showed faint staining of collagen type I in areas of trabecular meshwork with high MMP1 transgene expression.
conclusionsThe authors have developed a novel glucocorticoid-inducible adenovirus vector that overproduces MMP1 only in the presence of DEX. The availability of this vector sets up the foundation for the development of gene therapy drugs for the potential treatment of ocular hypertension in steroid-responsive patients.
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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.