ArticleInvestigative ophthalmology & visual science2011
Hypoxia-regulated retinal glial cell-specific promoter for potential gene therapy in disease.
Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays.International journal of molecular sciences · 2020Pooled it
- MicroRNA-124-3p Attenuated Retinal Neovascularization in Oxygen-Induced Retinopathy Mice by Inhibiting the Dysfunction of Retinal Neuroglial Cells through STAT3 Pathway.International journal of molecular sciences · 2023Article
- Molecular regulation of neuroinflammation in glaucoma: Current knowledge and the ongoing search for new treatment targets.Progress in retinal and eye research · 2022Review
- Review
- Emerging Concepts in Vector Development for Glial Gene Therapy: Implications for Leukodystrophies.Frontiers in cellular neuroscience · 2021Review
- Updates on Gene Therapy for Diabetic Retinopathy.Current diabetes reports · 2020Review
- AAV Targeting of Glial Cell Types in the Central and Peripheral Nervous System and Relevance to Human Gene Therapy.Frontiers in molecular neuroscience · 2020Review
- Cell-specific gene therapy driven by an optimized hypoxia-regulated vector reduces choroidal neovascularization.Journal of molecular medicine (Berlin, Germany) · 2018Article
- Assembly PCR synthesis of optimally designed, compact, multi-responsive promoters suited to gene therapy application.Scientific reports · 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
- Monomethyl fumarate promotes Nrf2-dependent neuroprotection in retinal ischemia-reperfusion.Journal of neuroinflammation · 2015Article
- A hypoxia-responsive glial cell-specific gene therapy vector for targeting retinal neovascularization.Investigative ophthalmology & visual science · 2014Article
- Drug and gene delivery to the back of the eye: from bench to bedside.Investigative ophthalmology & visual science · 2014Review
- Specific tools for targeting and expression in Müller glial cells.Molecular therapy. Methods & clinical development · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
purposeRetinal Müller cells span the retina and secrete several trophic factors and represent the functional link between blood vessels and neurons, making them attractive targets for gene therapy. Therefore, a hypoxia-regulated, retinal glial cell-specific vector was constructed and tested for its response to hypoxia.
methodsA hybrid promoter containing domains of human glial fibrillary acidic protein (GFAP) and several hypoxia-responsive and aerobically silenced elements (HRSE) was incorporated separately into plasmid vectors for generation of self-complementary adeno-associated virus. Müller cells trasfected with plasmids or virus were compared with other cell lines using standard
methodsThe mouse model of oxygen-induced retinopathy (OIR) was used to analyze retinas from mice exposed to high oxygen or room air to evaluate the induction of the regulated promoter.
resultsThe regulated promoter was silenced under aerobic conditions in comparison with unregulated promoter in Müller cells. Hypoxia induced a 12-fold and 16-fold increase in promoter activity in primary Müller cells and human Müller cell lines, respectively. In the OIR model, intravitreal injection of the regulated promoter at postnatal day 7 (P7) resulted in high levels of green fluorescent protein expression only in retinal Müller cells at P17. GFP expression was absent in retinas of mice only exposed to room air. In vivo studies confirm normoxia silencing, hypoxic induction, and cell specificity of the regulated promoter in the mouse retina.
conclusionsThis hypoxia-regulated, retinal glial cell-specific AAV vector provides a platform for gene therapy within regions of retinal hypoxia which are found in diabetic retinopathy and age-related macular degeneration.
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