Inhibition of choroidal neovascularization by blocking vascular endothelial growth factor receptor tyrosine kinase.
OBJECTIVE
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.
Kami
Junko
J
Department of Ophthalmology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Muranaka
Kimimasa
K
Department of Ophthalmology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Yanagi
Yasuo
Y
Department of Ophthalmology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Obata
Ryo
R
Department of Ophthalmology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. robata-tky@umin.ac.jp.
Tamaki
Yasuhiro
Y
Department of Ophthalmology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Shibuya
Masabumi
M
Department of Genetics, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002199:Capillary Permeability; D020256:Choroidal Neovascularization / Q000517:prevention & control*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005451:Fluorescein Angiography; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C116890:Semaxinib; C501163:Flt1 protein, mouse; D011505:Protein-Tyrosine Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2