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R. Albuquerque, W. Cho, S. Dridi, H. Kaneko, M. Kleinman, J. Baffi, J. Ambati; Endogenous VEGF-C Specifically Promotes Lymphangiogenesis in the Cornea. Invest. Ophthalmol. Vis. Sci. 2010;51(13):418.
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To determine whether endogenous VEGF-C, an established lymphangiogenesis molecule, has a physiologically relevant role in hemangiogenesis.
Wild-type and Vegfr2loxP/loxP mice were studied. We placed two intrastromal sutures were placed in the cornea for 2 weeks. sVEGFR-2 was ablated by in vivo transfection with Cre. Daily intraperitoneal injections of Vegfr-3 tyrosine kinase inhibitor or vehicle were performed in pCre-treated Vegfr2loxP/loxP mice after suture placement. VEGF-C neutralizing or isotype antibodies were injected intras[[Unsupported Character - Codename ­]]tromally twice weekly after suture placement. Corneal VEGF-C levels were quantified by ELISA following implantation of a recombinant VEGF-C micropellet, after suture placement, and in uninjured neonatal mice.
VEGF-C neutralization in the sutured corneas of wild-type mice resulted in inhibition of lymphangiogenesis (P < 0.05, n = 8) but not hemangiogenesis. Enhancement of suture-induced lymphangiogenesis by corneal ablation of sVEGFR-2 (a specific blocker of VEGF-C) was reduced by Vegfr-3 blockade. VEGF-C pellet placement resulted in levels of VEGF-C that were >100 times greater than endogenous VEGF-C levels following suture injury or even the endogenous VEGF-C levels at birth.
These data demonstrate that endogenous VEGF-C selectively promotes lymphangiogenesis in the cornea. Induction of hemangiogenesis by VEGF-C pellets reflects exaggerated, supraphysiological levels of growth factor that far exceed those attained in pathophysiologically relevant states.
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