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WE Philipp, L Speicher; Expression of Vascular Endothelial Growth Factors, Vegf-B, Vegf-C, Vegf-D, and of VegfC Receptors, Flt-4 (VEGFR-3) in Inflamed and Vascularized Human Corneas . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1755.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Vascular endothelial growth factors are key modulators of vasculogenesis and angiogenesis. VEGF-B, VEGF-C, and VEGF-D are newly discovered growth factors that show close homology to VEGF. Since VEGF and its receptors Flt-1 and Flk-1 are strongly expressed in vascularized corneas, we investigated the expression of VEGF-B, C, D, and of VEGF-C receptor, Flt-4 (VEGFR-3), in inflamed and vascularized human corneas to help define a possible role of these cytokines in the pathogenesis of corneal neovascularization. Methods: 26 vascularized human corneas were obtained at the time of penetrating keratoplasty in patients with various inflammatory corneal diseases. Immunohistochemistry was performed on frozen sections using the streptavidin-biotin-peroxidase method and antibodies against VEGF-B, C, D, Flt-4, and against von Willebrands factor to confirm the presence of neovascularization. Results: While only weak immunostaining for VEGF-B and VEGF-C was found on superficial corneal epithelial cells, all epithelial layers strongly stained with anti-VEGF-D antibody in corneas with chemical burns, herpetic stromal keratitis, atopic keratitis, zoster keratitis, fungal keratitis, and chronic allograft rejection. Flt-4 was strongly expressed on endothelial cells of limbal vessels, of newly formed vessels in the stroma, and interestingly, moderately on corneal endothelial cells. Conclusions: These results demonstrate that VEGF-D, and to a lesser extent also VEGF-B, VEGF-C, and VEGFR-3 are expressed in inflamed and vascularized human corneas and may play a role in the pathogenesis of corneal neovascularization.
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