ArticleJournal of molecular medicine (Berlin, Germany)2018
Cell-specific gene therapy driven by an optimized hypoxia-regulated vector reduces choroidal neovascularization.
Article in Journal of molecular medicine (Berlin, Germany), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Engineered virus-like particle-assembled Vegfa-targeting Cas9 ribonucleoprotein treatment alleviates neovascularization in wet age-related macular degeneration.Genome biology · 2025Article
- Dual VEGF-Targeting Strategy Via AAV2-Delivered sFLT-1 and shVEGF for Retinal Neovascularization Therapy.Investigative ophthalmology & visual science · 2025Article
- Engineered Feedback Employing Natural Hypoxia-Responsive Factors Enhances Synthetic Hypoxia Biosensors.ACS synthetic biology · 2025Article
- AAV-Based Strategies for Treatment of Retinal and Choroidal Vascular Diseases: Advances in Age-Related Macular Degeneration and Diabetic Retinopathy Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Regulatable Complement Inhibition of the Alternative Pathway Mitigates Wet Age-Related Macular Degeneration Pathology in a Mouse Model.Translational vision science & technology · 2023Article
- Delivery of nVEGFi using AAV8 for the treatment of neovascular age-related macular degeneration.Molecular therapy. Methods & clinical development · 2022Article
- From Bench to Bed: The Current Genome Editing Therapies for Glaucoma.Frontiers in cell and developmental biology · 2022Review
- Viral-Vector-Delivered Anti-Angiogenic Therapies to the Eye.Pharmaceutics · 2021Review
- IGFBP‑rP1‑silencing promotes hypoxia‑induced angiogenic potential of choroidal endothelial cells via the RAF/MEK/ERK signaling pathway.Molecular medicine reports · 2020Article
- The role of hypoxia-inducible factors in neovascular age-related macular degeneration: a gene therapy perspective.Cellular and molecular life sciences : CMLS · 2020Review
- Carbon Dots Fabrication: Ocular Imaging and Therapeutic Potential.Frontiers in bioengineering and biotechnology · 2020Review
- The Different Facades of Retinal and Choroidal Endothelial Cells in Response to Hypoxia.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Aberrant growth of blood vessels in the choroid layer of the eye, termed choroidal neovascularization (CNV), is the pathological hallmark of exudative age-related macular degeneration (AMD), causing irreversible blindness among the elderly. Co-localization of proangiogenic factors and hypoxia inducible factors (HIF) in neovascular membranes from AMD eyes suggests the role of hypoxia in pathogenesis of CNV. In order to utilize hypoxic conditions in RPE for therapeutic purposes, we developed an optimized hypoxia regulated, RPE cell-specific gene therapy to inhibit choroidal neovascularization. An adeno-associated virus (AAV2) vector comprising a RPE-specific promoter and HIF-1 response elements (HRE) was designed to regulate production of human endostatin (a powerful angiostatic protein) in RPE. The vector was tested in a mouse model of laser-induced CNV using subretinal delivery. Spectral domain optical coherence tomography (SD-OCT) images from live mice and confocal images from lectin stained RPE flat mount sections demonstrated reduction in CNV areas by 80% compared to untreated eyes. Quantitative real-time polymerase chain reaction (qPCR) confirmed exogenous endostatin mRNA expression from the regulated vector that was significantly elevated 3, 7, and 14 days following laser treatment, but its expression was completely shut off after 45 days. Thus, RPE-specific, hypoxia-regulated delivery of anti-angiogenic proteins could be a valuable therapeutic approach to treat neovascular AMD at the time and in the ocular space where it arises. KEY POINTS: An optimized gene therapy vector targeting hypoxia and tissue-specific expression has been designed. The inhibitory role of gene therapy vector was tested in a mouse model of laser-induced CNV. An 80% reduction in choroidal neovascularization was achieved by the optimized vector. The expression of endostatin was limited to retinal pigment epithelium and regulated by hypoxia.
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