Title

Spontaneous corneal hem- and lymphangiogenesis in mice with destrin-mutation depend on VEGFR3 signaling.

Document Type

Article

Publication Date

2005

Keywords

Aqueous-Humor, Comparative-Study, 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

JAX Source

Am J Pathol 2005 May; 166(5):1367-77.

Abstract

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.