April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Casitase B-lineage Lymphoma (c-Cbl) Pathway Regulates Pathological Angiogenesis
Author Affiliations & Notes
  • Deeba Husain
    Retina Service/Opthal,
    Boston Univ School of Medicine, Boston, Massachusetts
  • Eva Chou
    Department of Ophthalmology,
    Boston Univ School of Medicine, Boston, Massachusetts
  • Rosana D. Meyer
    Boston Univ School of Medicine, Boston, Massachusetts
  • Nader Rahimi
    Boston Univ School of Medicine, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Deeba Husain, None; Eva Chou, None; Rosana D. Meyer, None; Nader Rahimi, None
  • Footnotes
    Support  Lions Grant to dept of Ophthalmology. NIHR01EY017955-01A2 .
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4863. doi:
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      Deeba Husain, Eva Chou, Rosana D. Meyer, Nader Rahimi; Casitase B-lineage Lymphoma (c-Cbl) Pathway Regulates Pathological Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4863.

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

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Purpose: : c-Cbl has been identified as a negative regulator of PLC gamma 1 in endothelial cells. The biological significance and molecular mechanisms of c-Cbl is not known. This study is designed to study the effect of c-Cbl in three in vivo models of angiogenesis: cell proliferation assay, experimental choroidal neovascularization and tumor-induced angiogenesis model.

Methods: : Cell proliferation assay: c-Cbl null and wild type microvascular endothelial cells were prepared for in vitro angiogenesis. Cells were either unstimulated (-) or stimulated with VEGF (100ng/ml) and pictures were taken after 16 hours. Experimental choroidal neovascularization: Laser injury model was used in c -Cbl Null mice and wild mice. These eyes were imaged weekly with flourescein angiography for 4 weeks and the data was analyzed. Tumor Angiogenesis: c-Cbl null and wild Mice (4 animals for each experiment) were subcutaneously injected with Matrigel (10mg/ml) plus B16 melanoma cells (1x107). The tumor size was measured every 4 day for 12 days.

Results: : We found that loss of c-Cbl in endothelial cells promotes enhanced cell proliferation and angiogenesis in vitro. Loss of c-Cbl in mice leads to robust and sustained choroidal neovascularization. c-Cbl null mice showed larger and rapidly growing tumors.

Conclusions: : We propose c-Cbl is an angiogenic suppressor protein where upon activation it uniquely modulates PLC gamma1 activation by ubiquitination and subsequently inhibits VEGF-driven angiogenesis. Therefore this may offer a potential new target in the treatment of angiogenesis related diseases such as exudative macular degeneration.

Keywords: choroid: neovascularization • growth factors/growth factor receptors • retina 

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