May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Spontaneous Corneal Hem– and Lymphangiogenesis in Mice With Destrin–mutation Depend on VEGFR3–signaling
Author Affiliations & Notes
  • C. Cursiefen
    Department of Ophthalmology, University of Erlangen – Nurnberg, Erlangen, Germany
  • S. Ikeda
    Department of Medical Genetics, University of Wisconsin–Madison, Madison, WI
  • A. Ikeda
    Department of Medical Genetics, University of Wisconsin–Madison, Madison, WI
  • J.–S. Mo
    Schepens Eye Research Institute, Harvard Medical School, Boston, MA
  • R. Dana
    Schepens Eye Research Institute, Harvard Medical School, Boston, MA
  • F.E. Kruse
    Department of Ophthalmology, University of Erlangen – Nurnberg, Erlangen, Germany
  • B. Pytowski
    ImClone Systems, New York, NY
  • J.W. Streilein
    Schepens Eye Research Institute, Harvard Medical School, Boston, MA
  • Footnotes
    Commercial Relationships  C. Cursiefen, None; S. Ikeda, None; A. Ikeda, None; J. Mo, None; R. Dana, None; F.E. Kruse, None; B. Pytowski, ImClone Systems E; J.W. Streilein, None.
  • Footnotes
    Support  IZKF Erlangen (A9), DFG (Cu 47/1–2), ELAN (University of Erlangen)
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 4495. doi:
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      C. Cursiefen, S. Ikeda, A. Ikeda, J.–S. Mo, R. Dana, F.E. Kruse, B. Pytowski, J.W. Streilein; Spontaneous Corneal Hem– and Lymphangiogenesis in Mice With Destrin–mutation Depend on VEGFR3–signaling . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4495.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Lymphangiogenesis, i.e. the formation of new lymphatic vessels, is important for tumor metastasis and induction of immunity to peripheral antigens including organ transplants. Methods: We herein describe a novel mouse model of spontaneous, secondary lymphangiogenesis in the normally avascular cornea. Results: corn1 mice, which suffer from a deletion in the gene encoding the cytoskeletal protein destrin, besides hemangiogenesis also develop spontaneous outgrowth of LYVE–1+++/CD31+ lymphatic vessels into the cornea starting at age 4 weeks. Corneal lymphangiogenesis is delayed in onset, less intense and regresses earlier compared to 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, using this novel mouse model, a blocking anti–VEGFR3 antibody significantly inhibited not only lymph–, but also hemangiogenesis.Conclusions:In summary, a destrin deletion has differential effects on spontaneous hem– and lymphangiogenesis into the normally avascular cornea and represents a novel mouse model to study the mechanisms of lymphangiogenesis.

Keywords: neovascularization • cornea: basic science • growth factors/growth factor receptors 
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