May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Thrombospondin 1 Is an Endogenous Inhibitor of Inflammatory Lymphangiogenesis and Maintains Corneal Lymphangiogenic Privilege
Author Affiliations & Notes
  • C. Cursiefen
    Dept of Ophthalmology, University of Erlangen Nuernberg, Erlangen, Germany
  • F. Bock
    Dept of Ophthalmology, University of Erlangen Nuernberg, Erlangen, Germany
  • J. Onderka
    Dept of Ophthalmology, University of Erlangen Nuernberg, Erlangen, Germany
  • F. E. Kruse
    Dept of Ophthalmology, University of Erlangen Nuernberg, Erlangen, Germany
  • K. Maruyama
    Dept of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  • J. Lawler
    Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  • R. Dana
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • S. Masli
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships C. Cursiefen, None; F. Bock, None; J. Onderka, None; F.E. Kruse, None; K. Maruyama, None; J. Lawler, None; R. Dana, None; S. Masli, None.
  • Footnotes
    Support Interdisciplinary Center for Clinical Research (IZKF) Erlangen, ELAN Fonds Erlangen, DFG (German Research Council)
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3196. doi:https://doi.org/
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      C. Cursiefen, F. Bock, J. Onderka, F. E. Kruse, K. Maruyama, J. Lawler, R. Dana, S. Masli; Thrombospondin 1 Is an Endogenous Inhibitor of Inflammatory Lymphangiogenesis and Maintains Corneal Lymphangiogenic Privilege. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3196. doi: https://doi.org/.

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

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Abstract

Purpose:: Lymphangiogenesis, i.e. the outgrowth of new from preexisting lymph vessels, is an important early step in tumor metastasis and transplant host sensitization. Whereas with VEGF A, C and D at least some endogenous lymphangiogenic growth factors have been identified, so far no endogenous inhibitor of lymphangiogenesis is known.

Methods:: We tested the anti(hem)angiogenic factor thrombospondin (TSP) 1 for its antilymphangiogenic effect using the mouse model of inflammation-induced corneal neovascularization and TSP-deficient mice.

Results:: A significantly increased lymphangiogenic response was found in TSP 1-/- compared to wildtype mice. Furthermore, untreated TSP 1-/- mice displayed mild, spontaneous, isolated lymphangiogenesis. Sine TSP 1-/- mice had elevated corneal levels of the lymphangiogenic growth factor VEGF C, since monocytes are a prime source of VEGF C during inflammation and since the corneal stroma is endowed with numerous macrophages, we next examined the role of the monocytic TSP 1-receptor CD36 on inflammation induced lymphangiogenesis. CD36-/- mice displayed a significant increase in both inflammation-induced hem- and lymphangiogenesis. Since CD36 immunohistochemically was not expressed on ocular lymphatic vessels, but on resident corneal CD11b+ monocytic cells, an indirect antilymphangiogenic effect of TSP 1 via CD36-ligation on monocytes was hypothesized. Indeed, reconstitution of CD36-/- mice with wildtype bone-marrow reversed the lymphangiogenic phenotype of CD36-/- mice.

Conclusions:: We propose TSP 1 as endogenous inhibitor of (inflammation-induced) lymphangiogenesis, and suggest its mode of action to be indirectly via ligation of CD36 on bone-marrow derived monocytic cells. TSP 1 therefore contributes both to the "anti(lymph)angiogenic" privilege as well as the "immune" privilege of the cornea.#

Keywords: cornea: basic science • neovascularization • inflammation 
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