ArticleInvestigative ophthalmology & visual science2014
A hypoxia-responsive glial cell-specific gene therapy vector for targeting retinal neovascularization.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
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- Experiment-Based Interventions to Diabetic Retinopathy: Present and Advances.International journal of molecular sciences · 2022Review
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- A Review on Mesenchymal Stem Cells for Treatment of Retinal Diseases.Stem cell reviews and reports · 2021Review
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- Anti-Inflammatory (M2) Response Is Induced by a spFrontiers in immunology · 2021Article
- Updates on Gene Therapy for Diabetic Retinopathy.Current diabetes reports · 2020Review
- Carbon Dots Fabrication: Ocular Imaging and Therapeutic Potential.Frontiers in bioengineering and biotechnology · 2020Review
- CCAAT/Enhancer-Binding ProteinJournal of diabetes research · 2020Article
- Wnt Signaling in vascular eye diseases.Progress in retinal and eye research · 2019Review
- Novel stem cell and gene therapy in diabetic retinopathy, age related macular degeneration, and retinitis pigmentosa.International journal of retina and vitreous · 2019Review
- Diabetic retinopathy: a complex pathophysiology requiring novel therapeutic strategies.Expert opinion on biological therapy · 2018Review
- Cell-specific gene therapy driven by an optimized hypoxia-regulated vector reduces choroidal neovascularization.Journal of molecular medicine (Berlin, Germany) · 2018Article
- Spatially and Temporally RegulatedMolecular therapy. Methods & clinical development · 2017Article
- Targeting the Nrf2 Signaling Pathway in the Retina With a Gene-Delivered Secretable and Cell-Penetrating Peptide.Investigative ophthalmology & visual science · 2016Article
- Anti-VEGF therapy in the management of retinopathy of prematurity: what we learn from representative animal models of oxygen-induced retinopathy.Eye and brain · 2016Review
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4 authors at 2 institutions in 1 country.
Funding
Abstract
purposeMüller cells, the major glial cell in the retina, play a significant role in retinal neovascularization in response to tissue hypoxia. We previously designed and tested a vector using a hypoxia-responsive domain and a glial fibrillary acidic protein (GFAP) promoter to drive green fluorescent protein (GFP) expression in Müller cells in the murine model of oxygen-induced retinopathy (OIR). This study compares the efficacy of regulated and unregulated Müller cell delivery of endostatin in preventing neovascularization in the OIR model.
methodsEndostatin cDNA was cloned into plasmids with hypoxia-regulated GFAP or unregulated GFAP promoters, and packaged into self-complementary adeno-associated virus serotype 2 vectors (scAAV2). Before placement in hyperoxia on postnatal day (P)7, mice were given intravitreal injections of regulated or unregulated scAAV2, capsid, or PBS. Five days after return to room air, on P17, neovascular and avascular areas, as well as expression of the transgene and vascular endothelial growth factor (VEGF), were compared in OIR animals treated with a vector, capsid, or PBS.
resultsThe hypoxia-regulated, glial-specific, vector-expressing endostatin reduced neovascularization by 93% and reduced the central vaso-obliteration area by 90%, matching the results with the unregulated GFAP-Endo vector. Retinas treated with the regulated endostatin vector expressed substantial amounts of endostatin protein, and significantly reduced VEGF protein. Endostatin production from the regulated vector was undetectable in retinas with undamaged vasculature.
conclusionsThese findings suggest that the hypoxia-regulated, glial cell-specific vector expressing endostatin may be useful for treatment of neovascularization in proliferative diabetic retinopathy.
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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.