Bevacizumab as a Potent Inhibitor of Inflammatory Corneal Angiogenesis and Lymphangiogenesis

To analyze whether bevacizumab can inhibit inflammatory angiogenesis and lymphangiogenesis in the cornea. Bevacizumab (Avastin; Roche, Welwyn Garden City, UK) is a recombinant, humanized, monoclonal antibody against VEGF-A that has been approved by the U.S. Food and Drug Administration for the treat...

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Bibliographic Details
Published in:Investigative ophthalmology & visual science 2007-06, Vol.48 (6), p.2545-2552
Main Authors: Bock, Felix, Onderka, Jasmine, Dietrich, Tina, Bachmann, Bjorn, Kruse, Friedrich E, Paschke, Matthias, Zahn, Grit, Cursiefen, Claus
Format: Article
Language:English
Subjects:
Administration, Topical
Angiogenesis Inhibitors - therapeutic use
Animals
Antibodies, Monoclonal - therapeutic use
Antibodies, Monoclonal, Humanized
Bevacizumab
Biological and medical sciences
Blotting, Western
Bromodeoxyuridine - metabolism
Cell Proliferation - drug effects
Corneal Neovascularization - drug therapy
Disease Models, Animal
Endothelial Cells - drug effects
Endothelial Cells - pathology
Enzyme-Linked Immunosorbent Assay
Eye and associated structures. Visual pathways and centers. Vision
Female
Fundamental and applied biological sciences. Psychology
Glycoproteins - metabolism
Lymphangiogenesis - drug effects
Mice
Mice, Inbred BALB C
Platelet Endothelial Cell Adhesion Molecule-1 - metabolism
Surface Plasmon Resonance
Vascular Endothelial Growth Factor A - antagonists & inhibitors
Vertebrates: nervous system and sense organs
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Summary:To analyze whether bevacizumab can inhibit inflammatory angiogenesis and lymphangiogenesis in the cornea. Bevacizumab (Avastin; Roche, Welwyn Garden City, UK) is a recombinant, humanized, monoclonal antibody against VEGF-A that has been approved by the U.S. Food and Drug Administration for the treatment of colon carcinomas. The mouse model of suture-induced corneal neovascularization was used to assess the antihemangiogenic and antilymphangiogenic effect of bevacizumab by systemic and topical application. Corneal flatmounts were stained with LYVE-1 as a specific lymphatic vascular endothelial marker and CD31 as a pan-endothelial marker, and blood and lymph vascularized areas were analyzed morphometrically. The inhibitory effect of bevacizumab on lymphatic endothelial cells (LECs) was analyzed with a colorimetric (BrdU) proliferation ELISA. The binding ability of bevacizumab to murine VEGF-A was analyzed by Western blot, ELISA, and surface plasmon resonance. The systemic and topical applications of bevacizumab significantly inhibited the outgrowth of blood (P < 0.006 and P < 0.0001, respectively) and lymphatic (P < 0.002 and P < 0.0001, respectively) vessels. Inhibition of the proliferation of LECs was also significant (P < 0.0001). Western blot analysis, ELISA, and the surface plasmon resonance assay showed that bevacizumab binds murine VEGF-A. Topical or systemic application of bevacizumab inhibits both inflammation-induced angiogenesis and lymphangiogenesis in the cornea. This finding suggests an important role of VEGF-A in corneal lymphangiogenesis. Bevacizumab may be useful in preventing immune rejections after penetrating keratoplasty or tumor metastasis via lymphatic vessels.
ISSN:0146-0404
1552-5783
1552-5783
DOI:10.1167/iovs.06-0570