The Role of TNF--Receptors in Angiogenesis and Lymphangiogenesis in Corneal Neovascularization

Abstract

Purpose: : Tumor necrosis factor alpha (TNF-α) is a pleiotropic proinflammatory cytokine. This study was conducted to investigate the role of TNF-α-receptors (TNF-Rp-55 and TNF-Rp-75) in angiogenesis and lymphangiogenesis in corneal neovascularization in vivo.

Methods: : Corneal neovascularization was induced in TNF-Rp55- and TNF-Rp75-deficient mice, as well as in their respective wild-types, by suturing three 11-0 nylon intrastromally in the cornea in a standardized manner. Blood and lymph vascularized areas of corneal flatmounts were analyzed 14 days after suturing by using double immunofluorescence (with CD31 as a panendothelial and LYVE-1 as a lymphatic vascular endothelium-specific marker) and measured with a NIH image program.

Results: : Corneal neovascularization of TNF-Rp-55- and TNF-Rp-75-deficient mice showed differences in angiogenesis and in lymphangiogenesis. The lymph vascularized areas in the TNF-Rp-55-deficient mice were almost 40% smaller in comparison to the wild-types. On the contrast the TNF-Rp-75-deficient mice demonstrated similar lymph vascularized areas compared to the control group. There were no differences between the three groups in the blood vascularized areas.

Conclusions: : TNF-Rp-55 and TNF-Rp-75 probably play differential roles in lymphangiogenesis and angiogenesis in corneal neovascularization. The exact mechanism of TNF-α-receptors on corneal neovascularization remains to be studied.

Keywords: neovascularization • growth factors/growth factor receptors • transgenics/knock-outs