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M. Kitamura, S. He, S. Sonoda, C. Spee, S. J. Ryan, D. R. Hinton; Expression of Vascular Endothelial Growth Factor Receptor-3 in Laser-Induced Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2344.
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To determine the expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in the murine model of laser induced choroidal neovascularization (CNV) and the regulation of VEGFR-3 by inflammatory cytokines in human RPE cells in vitro.
Cultured fetal human RPE cells were used for the study. VEGFR-3 mRNA expression was determined by RT-PCR. VEGFR-3 protein in supernatant and cell lysate was examined by western blotting. RPE cells were exposed to tert-butyl-hydroperoxide (TBH), IFN-γ and TNF- from 24~72 hours. The regulation of expression of VEGFR-3 in RPE was analyzed by western blotting. The expression of VEGFR-3 in human fetal, and adult retinal sections and murine CNV sections was evaluated by immunohistochemistry.
Human RPE cells express VEGFR-3 mRNA and protein. VEGFR-3 was detected in choroidal capillaries in fetal retina and RPE monolayer of adult retinal sections. IFN-γ increased the secretion of soluble VEGFR-3 protein in the culture medium. TBH decreased the secretion of solubleVEGFR-3 protein. Prominent immunoreactivity for VEGFR-3 was detected within laser-induced CNV membranes.
Levels of soluble VEGFR-3 in cultured RPE cell media is regulated by IFN-γ and TBH. VEGFR-3 is expressed in laser induced CNV membranes in the mouse. The result suggests that VEGFR-3 may play an important role in the pathogenesis of CNV.
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