ArticleGene therapy2016
Inducible scAAV2.GRE.MMP1 lowers IOP long-term in a large animal model for steroid-induced glaucoma gene therapy.
Article in Gene therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Challenging glaucoma with emerging therapies: an overview of advancements against the silent thief of sight.Frontiers in medicine · 2025Review
- Gene therapy for glaucoma: Targeting key mechanisms.Vision research · 2024Review
- Engineered sensor actuator modulator as aqueous humor outflow actuator for gene therapy of primary open-angle glaucoma.Journal of translational medicine · 2024Article
- Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists.International journal of molecular sciences · 2024Article
- The concept of gene therapy for glaucoma: the dream that has not come true yet.Neural regeneration research · 2024Review
- Therapeutic strategies for glaucoma and optic neuropathies.Molecular aspects of medicine · 2023Review
- Review
- Matrix metalloproteinase-3 (MMP-3)-mediated gene therapy for glaucoma.Science advances · 2023Article
- Evaluation of trabecular meshwork-specific promotersInternational journal of ophthalmology · 2023Article
- Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres.Drug delivery · 2021Article
- Long-Term Decrease of Intraocular Pressure in Rats by Viral Delivery of miR-146a.Translational vision science & technology · 2021Article
- A 2020 vision of ocular gene therapy.Gene therapy · 2021Article
- Looking into the future: Gene and cell therapies for glaucoma.Veterinary ophthalmology · 2021Review
- Generation of a Matrix Gla (Mgp) floxed mouse, followed by conditional knockout, uncovers a new Mgp function in the eye.Scientific reports · 2020Article
- C3 Transferase-Expressing scAAV2 Transduces Ocular Anterior Segment Tissues and Lowers Intraocular Pressure in Mouse and Monkey.Molecular therapy. Methods & clinical development · 2020Article
- Transduction optimization of AAV vectors for human gene therapy of glaucoma and their reversed cell entry characteristics.Gene therapy · 2020Article
- Gene Therapy for Glaucoma by Ciliary Body Aquaporin 1 Disruption Using CRISPR-Cas9.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Glucocorticoid-Induced Ocular Hypertension: Origins and New Approaches to Minimize.Expert review of ophthalmology · 2020Article
- Transduction Pattern of AAVs in the Trabecular Meshwork and Anterior-Segment Structures in a Rat Model of Ocular Hypertension.Molecular therapy. Methods & clinical development · 2019Article
- Lentiviral Vector-Mediated Expression of Exoenzyme C3 Transferase Lowers Intraocular Pressure in Monkeys.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Current treatment of glaucoma relies on administration of daily drops or eye surgery. A gene therapy approach to treat steroid-induced glaucoma would bring a resolution to millions of people worldwide who depend on glucocorticoid therapy for a myriad of inflammatory disorders. Previously, we had characterized a short-term Adh.GRE.MMP1 gene vector for the production of steroid-induced MMP1 in the trabecular meshwork and tested reduction of elevated intraocular pressure (IOP) in a sheep model. Here we conducted a trial transferring the same transgene cassette to a clinically safe vector (scAAV2), and extended the therapeutic outcome to longer periods of times. No evidence of ocular and/or systemic toxicity was observed. Viral genome distributions showed potential reinducible vector DNAs in the trabecular meshwork (0.4 v.g. per cell) and negligible copies in six major internal organs (0.00002-0.005 v.g. per cell). Histological sections confirmed successful transduction of scAAV2.GFP to the trabecular meshwork. Optimization of the sheep steroid-induced hypertensive model revealed that topical ophthalmic drug difluprednate 0.05% (durezol) induced the highest IOP elevation in the shortest time. This is the first efficacy/toxicity study of a feasible gene therapy treatment of steroid-induced hypertension using clinically accepted self-complementary adeno-associated vectors (scAAV) vectors in a large animal model.
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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.