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An Ex Vivo Choroid Sprouting Assay of Ocular Microvascular Angiogenesis
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Endogenous endostatin inhibits choroidal neovascularization.

Alexander G Marneros1, Haicheng She, Hadi Zambarakji

  • 1Department of Developmental Biology, Harvard School of Dental Medicine, 188 Longwood Ave., Boston, MA 02115, USA. alexander_marneros@yahoo.com

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|May 29, 2007
PubMed
Summary

Endogenous endostatin inhibits pathological angiogenesis, like choroidal neovascularization (CNV). Supplementing endostatin significantly reduced CNV growth and leakage in mice, suggesting therapeutic potential.

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Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Pathology

Background:

  • Endostatin, derived from collagen XVIII, shows antiangiogenic effects at high doses.
  • The role of endogenous endostatin at physiological levels in inhibiting pathological angiogenesis, such as choroidal neovascularization (CNV), remains unclear.

Purpose of the Study:

  • To investigate the role of endogenous endostatin in inhibiting pathological angiogenesis, specifically CNV.
  • To evaluate the therapeutic potential of endostatin in treating CNV.

Main Methods:

  • Induced CNV in mice lacking collagen XVIII/endostatin and in control mice using a laser injury model.
  • Administered recombinant endostatin to deficient and control mice.
  • Performed ultrastructural analysis of choroidal vasculature.

Main Results:

  • CNV lesions in mice lacking endostatin were approximately 3-fold larger with increased vascular leakage compared to controls.
  • Recombinant endostatin administration reduced CNV lesion size and vascular leakage in deficient mice.
  • Recombinant endostatin almost completely inhibited CNV in control mice.

Conclusions:

  • Endogenous endostatin acts as an inhibitor of induced angiogenesis.
  • Exogenous endostatin potently inhibits CNV growth and vascular leakage.
  • Endostatin holds therapeutic promise for inhibiting CNV pathogenesis.