Abstract
Purpose:
To investigate the role played by receptors of vascular endothelial growth factors, Flt-1 and KDR/Flk-1, on an experimental model of choroidal neovascularization (CNV).
Methods:
The vascular endothelial growth factor-A (VEGF-A) receptor-specific tyrosine kinase inhibitor SU5416 was administered to a laser-induced mouse model of CNV. The formation of CNV and the degree of vascular permeability in Flt-1 tyrosine kinase domain-deficient mice were also investigated.
Results:
SU5416 reduced vascularity and vascular endothelial cell proliferation, and promoted endothelial cell apoptosis within CNV. Furthermore, the formation of CNV and the degree of vascular permeability were significantly reduced in Flt-1 tyrosine kinase domain-deficient mice, and this effect was enhanced by the administration of SU5416.
Conclusions:
Both Flt-1 and KDR/Flk-1 have a significant role in CNV formation. Suppression of apoptosis may be involved in the process.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / pharmacology*
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Animals
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Apoptosis / drug effects
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Capillary Permeability
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Choroidal Neovascularization / prevention & control*
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Disease Models, Animal
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Endothelium, Vascular / pathology
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Female
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Fluorescein Angiography
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Immunoenzyme Techniques
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In Situ Nick-End Labeling
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Indoles / pharmacology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Pyrroles / pharmacology*
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Vascular Endothelial Growth Factor A / physiology
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Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors*
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Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
Substances
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Angiogenesis Inhibitors
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Indoles
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Pyrroles
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Vascular Endothelial Growth Factor A
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vascular endothelial growth factor A, mouse
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Semaxinib
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Flt1 protein, mouse
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Protein-Tyrosine Kinases
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factor Receptor-2