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F. Bock, J. Onderka, T. Dietrich, B. Bachmann, F. Kruse, C. Cursiefen; Bevacizumab (Avastin) as a Potent Inhibitor of Inflammatory Hem– and Lymphangiogenesis in the Cornea . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3908.
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Bevacizumab (Avastin®) is a recombinant, humanized, monoclonal anti–VEGF antibody. By inhibiting vascular endothelial growth factors (VEGF) tumor growth can be suppressed and this drug therefore is used in the treatment of colon carcinomas. Purpose of this study was to analyze whether Avastin can inhibit inflammatory ingrowth of hem– and lymphangiogenesis in the cornea.
In a mouse model of suture induced inflammatory corneal neovascularization we analyzed the effects of systemic application of Bevacizumab. Three interrupted 11–0 nylon sutures were placed into the corneal stroma of BALB/c mice (6 weeks old) and left in place for seven days to induce neovascularization. The treatment group (n=9) received Bevacizumab intraperitoneally at day of surgery and three days later (0.1 mg in 500µl/mouse). Control mice received an equal volume of saline solution. After seven days, mice were sacrificed and corneal whole mounts prepared. For immunohistochemistry, corneal flat mounts were stained with LYVE–1 as a specific lymphatic vascular endothelial marker and CD31 as panendothelial marker. Morphometry of blood and lymphatic vessels was performed with the image analysis software analySIS^B (Soft Imaging Systems GmbH, Münster, Germany).
Morphometrical analysis was performed with an improved analysing method based on grey filter sampling to gain more objectivity and precision. The application of Avastin inhibited the outgrowth of blood vessels significant (P < 0.006) in comparison to the control. The outgrowth of lymphatic vessels was also inhibited significant (P< 0.002).
The anti–angiogenic drug Bevacizumab can inhibit the inflammatory outgrowths of blood vessels in the cornea. Interesting is the additional inhibition of lymphangiogenesis in the cornea. Bevacizumab seems to have the ability to restrain the formation of the afferent and efferent arm of the "immune reflex arc" and therefore could be used for anti–angiogenic therapies pre– and post–keratoplasty to promote graft survival.
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