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E.-S. Chung, R. Dana; Differential Effects of VEGF-C versus Mutant (Cys156Ser) VEGF-C on Murine Corneal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1751.
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Vascular endothelial growth factor (VEGF) receptor-3 (VEGFR-3) activation by its ligand VEGF-C is necessary for lymphangiogenesis in adults; however, mature VEGF-C has affinity for both VEGFR-2 and VEGFR-3 whereas mutant (Cys156Ser) VEGF-C (VEGF-Cm) is a selective agonist of VEGFR-3 [Joukov V, 1998; Rissanen TT, 2003], thereby theoretically leading to different degrees of blood and lymph vessel growth. The purpose of this study was to investigate the differential effect of VEGF-R2/3 binding by VEGF-C versus selective activation of VEGFR-3 with VEGF-Cm in induction of blood and lymph vessels in the mouse cornea.
Recombinant VEGF-C and VEGF-Cm (R&D systems) pellets at two different concentrations (20ng and 80ng) were implanted in 6-week old BALB/c murine cornea. Slit lamp photographs were taken at 1 and 2 weeks to grade the induced vessels. At 2 weeks, mice were sacrificed and whole mount preparations of the corneas were prepared for immunohistochemical staining of CD-31hiLYVE-1- blood vessels and CD-31loLYVE-1+ lymphatics. Slit lamp photographs and fluorescence microscopic pictures were analyzed with NIH Image J software.
There was a trend toward lower blood vessel induction and higher lymphatic vessel induction with VEGF-Cm compared to VEGF-C at a low (20ng) concentration; however, at high concentration (80ng) there was no statistically significant differences in the degree of induced blood vessels or lymphatic vessels between the VEGF-C and VEGF-Cm pellet-implanted corneas.
Selective activation of VEGFR-3 with VEGF-Cm induced not only lymph vessels but also blood vessels in the murine corneal micropocket assay, suggesting that activation of VEGFR-3 alone by VEGF-Cm can have a significant role in blood vessel growth, especially at high concentrations. Taken together, these data further implicate VEGFR-3 in angiogenesis beyond its well-recognized role in lymphangiogenesis.
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