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D. Hos, F. Bock, D. R. Saban, B. Regenfuss, J. Onderka, S. Masli, R. Dana, C. Cursiefen; Corticosteroids Inhibit Inflammatory Corneal Lymphangigenesis in vivo, but Display Proangiogenic Properties in vitro. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5695.
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© ARVO (1962-2015); The Authors (2016-present)
Corticosteroids are widely used as potent anti-inflammatory drugs for the treatment of various corneal diseases. Purpose of this work was to analyze whether topical application of corticosteroids inhibits inflammatory corneal lymphangiogenesis. Furthermore, we wanted to analyze which mechanisms underlie this effect.
Inflammatory murine corneal neovascularization was induced by suture placement, corneas were then treated with topical Fluorometholone, Prednisolone or Dexamethasone. After one week, corneas were prepared and stained with LYVE-1 as a lymphatic endothelial specific marker. Pathological lymphangiogenesis was then detected semi-automatically on digitized whole mounts. The effect of corticosteroids on F4/80+ CD11b+ macrophage recruitment in vivo was assessed via immunohistochemistry and FACS analysis. The in vitro effect of corticosteroids on proinflammatory cytokine expression by macrophages (peritoneal exudate cells) was tested via real time PCR analysis.
Topical treatment with corticosteroids resulted in a significant reduction of inflammatory corneal lymphangiogenesis (p<0.001). The antilymphangiogenic effect of Fluorometholone was significantly weaker than that of Prednisolone and Dexamethasone (p<0.01). The recruitment of macrophages into the inflamed cornea was significantly inhibited by topical application of all corticosteroids ((p<0.001). Conversely, in vitro treatment of PECs with corticosteroids led to a significant upregulation of the expression levels of VEGF-A, VEGF-C and VEGF-D.
Corticosteroids are strong inhibitors of inflammatory corneal lymphangiogenesis in vivo, with significant differences between various corticosteroids in terms of their antilymphangiogenic potency. The main mechanism of the antilymphangiogenic effect seems to be through the strong inhibition of macrophage recruitment. However, corticosteroids also display proangiogenic effects, at least in vitro.
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