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Wolfgang Philipp, Lilly Speicher, Christian Humpel; Expression of Vascular Endothelial Growth Factor and Its Receptors in Inflamed and Vascularized Human Corneas. Invest. Ophthalmol. Vis. Sci. 2000;41(9):2514-2522.
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purpose. To help further define the possible role of vascular endothelial growth
factor (VEGF) in the pathogenesis of corneal neovascularization,
the expression of VEGF and of its receptors Flt-1 and Flk-1 was
investigated in various inflammatory corneal diseases.
methods. Polyclonal antibodies to VEGF and its receptors were used for
immunohistochemical staining of frozen sections of 38 human corneas
with various degrees of neovascularization and inflammation. In
addition, a panel of monoclonal antibodies was used to characterize the
composition of the inflammatory infiltrates and to confirm the presence
of neovascularization. Furthermore, VEGF concentrations were determined
in vascularized corneas using a sensitive enzyme-linked immunosorbent
results. VEGF was expressed by epithelial cells, by corneal endothelial cells,
by vascular endothelial cells of limbal vessels and of newly formed
vessels in the stroma, and weakly by keratocytes. Furthermore, VEGF
expression was often markedly increased in inflamed corneas on
epithelial cells and on vascular endothelial cells, particularly in the
vicinity of macrophage infiltrates, and on fibroblasts in scar tissue.
Correspondingly, VEGF concentrations were significantly higher in
vascularized corneas compared with normal control corneas
(P < 0.001). Expression of both VEGF receptors,
Flt-1 and Flk-1, was increased on endothelial cells of newly formed
vessels in the stroma of inflamed corneas compared with limbal vessels
of normal control corneas. In addition, Flt-1 was also expressed by
corneal endothelial cells and by macrophages, whereas Flk-1 expression
conclusions. These results demonstrate that VEGF, Flt-1, and Flk-1 are strongly
expressed in inflamed and vascularized human corneas and, thus, may
play an important role in corneal
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