Inhibition of choroidal neovascularization by blocking vascular endothelial growth factor receptor tyrosine kinase
- 134 Downloads
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).
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.
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.
Both Flt-1 and KDR/Flk-1 have a significant role in CNV formation. Suppression of apoptosis may be involved in the process.
Key Wordsapoptosis choroidal neovascularization SU5416 tyrosine kinase receptor-1 vascular endothelial growth factor-A
Unable to display preview. Download preview PDF.
- 1.Leibowitz HM, Krueger DE, Maunder LR, et al. The Framingham Eye Study monograph: an ophthalmological and epidemiological study of cataract, glaucoma, diabetic retinopathy, macular degeneration, and visual acuity in a general population of 2631 adults, 1973–1975. Surv Ophthalmol 1980;24:335–610.CrossRefPubMedGoogle Scholar
- 8.Iwashita K, Takahashi K, Wada M, Uyama M. Vascular endothelial growth factor promotes experimental choroidal neovascularization in monkey eyes (in Japanese with English abstract). Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 1999;103:415–424.Google Scholar
- 14.Shibuya M, Ito N, Claesson-Welsh L. Structure and function of VEGF Receptor-1 and-2. Curr Topics Microbiol Immunol 1999;237:59–83.Google Scholar
- 32.Gupta K, Ramakrishnan S, Browne PV, Solovey A, Hebbel RP. A novel technique for culture of human dermal microvascular endothelial cells under either serum-free or serum-supplemented conditions: isolation by panning and stimulation with vascular endothelial growth factor. Exp Cell Res 1997;230:244–251.CrossRefPubMedGoogle Scholar