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Lymphangiogenesis, the formation of new lymphatic vessels, is important for tumor metastasis and induction of immunity to peripheral antigens including organ transplants. We herein describe a novel mouse model of spontaneous, secondary lymphangiogenesis in the normally avascular cornea. corn1 mice, which suffer from a deletion in the gene encoding the cytoskeletal protein destrin, develop hemangiogenesis as well as spontaneous outgrowth of LYVE-1+++/CD31+ lymphatic vessels into the cornea starting at age 4 weeks. Corneal lymphangiogenesis is delayed in onset, is less intense, and regresses earlier compared with hemangiogenesis. Moreover, the lymphangiogenesis is preceded only by a mild recruitment of CD45+ inflammatory cells into the cornea. In contrast to mice with inflammation-induced hem- and lymphangiogenesis, corn1 mice do not develop breakdown of the blood-aqueous barrier. Finally, in this novel mouse model, a blocking anti-VEGFR3 antibody significantly inhibited not only lymph- but also hemangiogenesis. In summary, destrin deletion has differential effects on spontaneous hem- and lymphangiogenesis in the normally avascular cornea and represents a novel mouse model to study the mechanisms of lymphangiogenesis and to test the antihem- and antilymphangiogenic properties of known or new antiangiogenic agents.

Original publication

DOI

10.1016/S0002-9440(10)62355-3

Type

Journal article

Journal

Am J Pathol

Publication Date

05/2005

Volume

166

Pages

1367 - 1377

Keywords

Actin Depolymerizing Factors, Animals, Aqueous Humor, Cornea, Destrin, Eye Proteins, Growth Substances, Leukocyte Count, Limbus Corneae, Lymphangiogenesis, Lymphatic System, Mice, Microfilament Proteins, Mutation, Neovascularization, Physiologic, Protein Isoforms, RNA, Messenger, Signal Transduction, Time Factors, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-3