April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Exogeneous Thrombospondin 1 Inhibits Inflammatory Corneal Lymphangiogenesis in-vivo
Author Affiliations & Notes
  • Felix Bock
    Department of Opthalmology, University Erlangen-Nuremberg, Erlangen, Germany
  • Kazuichi Maruyama
    Ophthalmology, Kyoto Prefectural Univ of Med, Kamigyo-ku, Japan
  • Daniel R. Saban
    Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts
  • Zahra Sadrai
    Ophthalmology/Harvard Med Sch, Schepens Eye Research Institute, Boston, Massachusetts
  • Jack Lawler
    Dept. of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  • Sharmila Masli
    Ophthalmology/Harvard Med Sch, Schepens Eye Research Institute, Boston, Massachusetts
  • Reza Dana
    MEEI/SERI Harvard Ophthalmology, Boston, Massachusetts
  • Claus Cursiefen
    Dept of Ophthalmology, University of Erlangen Nuernberg, Erlangen, Germany
  • Footnotes
    Commercial Relationships  Felix Bock, None; Kazuichi Maruyama, None; Daniel R. Saban, None; Zahra Sadrai, None; Jack Lawler, None; Sharmila Masli, None; Reza Dana, None; Claus Cursiefen, None
  • Footnotes
    Support  DFG (Special Research Programm (SFB) 643 (TP B10), NIH EY10765, NIH EY15472, Interdisciplinary Center for Clinical Research (IZKF) Erlangen (A9)
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 6405. doi:
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      Felix Bock, Kazuichi Maruyama, Daniel R. Saban, Zahra Sadrai, Jack Lawler, Sharmila Masli, Reza Dana, Claus Cursiefen; Exogeneous Thrombospondin 1 Inhibits Inflammatory Corneal Lymphangiogenesis in-vivo. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6405.

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

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Purpose: : Lymphangiogenesis, i.e. the outgrowth of new from preexisting lymph vessels, is an important early step in tumor metastasis and transplant host sensitization. We have recently demonstrated, that TSP-1 maintains the lymphangiogenic privilege of the cornea. Aim of this study was to elucidate the molecular mechanism of the antilymphangiogenic effect of TSP-1 and to assess the therapeutic potential of TSP-1 as topical, antilymphangiogenic drug at the ocular surface.

Methods: : We used murine peritoneal exudate cell (PEC) cultures from CD36-/- and WT mice for real time PCR and protein ELISAs. To test the antilymphangiogenic effect of thrombospondin in-vivo we used the mouse model of inflammation-induced corneal neovascularization and rhTSP-1.

Results: : TSP-1 down regulates the VEGF-C expression in macrophages via the receptor CD36. Thereby TSP-1 antagonises the prolymphangiogenic effect of activated TGFβ. In TSP-1-/- mice the absence of the VEGF-C homeostatsis in corneal macrophages leads to VEGF-C accumulation and successively to an increase of corneal macrophages which leads to spontaneous lymphangiogenesis in TSP-1 KO mice not only in the cornea but also in e.g. the skin. Functionally, we could significantly reduce the lymphangiogenesis in inflamed corneas using rhTSP-1 as eye drops.

Conclusions: : TSP-1 is an endogenous inhibitor of (inflammation-induced) lymphangiogenesis via the ligation of CD36 on bone-marrow derived monocytic cells. The topical use of rhTSP-1 as an antilymphangiogenic drug could be beneficial for corneal transplantation by hampering the invasion of macrophages and reducing the ingrowth of antigen transporting lymphatic vessels.

Keywords: cornea: basic science • neovascularization • inflammation 

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