This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cursiefen, C. Articles by Streilein, J. W. Search for Related Content PubMed PubMed Citation Articles by Cursiefen, C. Articles by Streilein, J. W.

(American Journal of Pathology. 2005;166:1367-1377.)
© 2005 American Society for Investigative Pathology

Spontaneous Corneal Hem- and Lymphangiogenesis in Mice with Destrin-Mutation Depend on VEGFR3 Signaling

Claus Cursiefen^*, Sakae Ikeda, Patsy M. Nishina, Richard S. Smith, Akihiro Ikeda, David Jackson^¶, Jun-Song Mo, Lu Chen, M. Reza Dana, Bronislaw Pytowski^||, Friedrich E. Kruse^* and J. Wayne Streilein

From the Department of Ophthalmology,^* Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; The Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts; The Jackson Laboratory, Bar Harbor, Maine; the Department of Medical Genetics, University of Wisconsin, Madison, Wisconsin; MRC Human Immunology,^¶ Oxford, United Kingdom; and ImClone Systems,|| New York, New York

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.

This article has been cited by other articles:

				D. Hos, F. Bock, T. Dietrich, J. Onderka, F. E. Kruse, K.-H. Thierauch, and C. Cursiefen Inflammatory Corneal (Lymph)angiogenesis Is Blocked by VEGFR-Tyrosine Kinase Inhibitor ZK 261991, Resulting in Improved Graft Survival after Corneal Transplantation Invest. Ophthalmol. Vis. Sci., May 1, 2008; 49(5): 1836 - 1842. [Abstract] [Full Text] [PDF]

				F. Bock, J. Onderka, T. Dietrich, B. Bachmann, F. E. Kruse, M. Paschke, G. Zahn, and C. Cursiefen Bevacizumab as a Potent Inhibitor of Inflammatory Corneal Angiogenesis and Lymphangiogenesis Invest. Ophthalmol. Vis. Sci., June 1, 2007; 48(6): 2545 - 2552. [Abstract] [Full Text] [PDF]

				H. Xu, M. Chen, D. M. Reid, and J. V. Forrester LYVE-1-Positive Macrophages Are Present in Normal Murine Eyes Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2162 - 2171. [Abstract] [Full Text] [PDF]