ArticleInvestigative ophthalmology & visual science2012
Inhibition of choroidal and corneal pathologic neovascularization by Plgf1-de gene transfer.
Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Sustained and Efficient Delivery of Antivascular Endothelial Growth Factor by the Adeno-associated Virus for the Treatment of Corneal Neovascularization: An Outlook for Its Clinical Translation.Journal of ophthalmology · 2024Review
- Nanotechnology-based ocular drug delivery systems: recent advances and future prospects.Journal of nanobiotechnology · 2023Review
- Gene Therapy in the Anterior Eye Segment.Current gene therapy · 2022Review
- 4-(2-Butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid inhibits angiogenesisFrontiers in cardiovascular medicine · 2022Article
- Review
- Co-inhibition of PGF and VEGF blocks their expression in mononuclear phagocytes and limits neovascularization and leakage in the murine retina.Journal of neuroinflammation · 2019Article
- Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases.Acta ophthalmologica · 2018Review
- Osmotic induction of placental growth factor in retinal pigment epithelial cells in vitro: contribution of NFAT5 activity.Molecular biology reports · 2016Article
- AAV2 delivery of Flt23k intraceptors inhibits murine choroidal neovascularization.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Enhanced wound healing, kinase and stem cell marker expression in diabetic organ-cultured human corneas upon MMP-10 and cathepsin F gene silencing.Investigative ophthalmology & visual science · 2013Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeOcular neovascularization (NV), the primary cause of blindness, typically is treated via inhibition of VEGF-A activity. However, besides VEGF-A, other proteins of the same family, including VEGF-B and placental growth factor (PlGF, all together VEGFs), have a crucial role in the angiogenesis process. PlGF and VEGF, which form heterodimers if co-expressed, both are required for pathologic angiogenesis. We generated a PlGF1 variant, named PlGF1-DE, which is unable to bind and activate VEGFR-1, but retains the ability to form heterodimer. PlGF1-DE acts as dominant negative of VEGF-A and PlGF1wt through heterodimerization mechanism. The purpose of our study was to explore the therapeutic potential of Plgf1-de gene in choroid and cornea NV context.
methodsIn the model of laser-induced choroidal neovascularization (CNV), Plgf1-de gene, and as control Plgf1wt, LacZ, or gfp genes, were delivered using adeno-associated virus (AAV) vector by subretinal injection 14 days before the injury. After 7 days CNV volume was assessed. Corneal NV was induced by scrape or suture procedures. Expression vectors for PlGF1wt or PlGF1-DE, and as control the empty vector pCDNA3, were injected in the mouse cornea after the vascularization insults. NV was evaluated with CD31 and LYVE-1 immunostaining.
resultsThe expression of Plgf1-de induced significant inhibition of choroidal and corneal NV by reducing VEGF-A homodimer production. Conversely, the delivery of Plgf1wt, despite induced similar reduction of VEGF-A production, did not affect NV.
conclusionsPlgf1-de gene is a new therapeutic tool for the inhibition of VEGFs driven ocular NV.
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Registered trials
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