May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Genetic Deletion or Pharmacological Inhibition of Angiopoietin-2 Reduces Injury-Induced Corneal Neovascularization, Lymphangiogenesis and Inflammation
Author Affiliations & Notes
  • J. Cao
    Ophthalmology, Regeneron Pharmaceuticals Inc, Tarrytown, New York
  • Y. Liu
    Ophthalmology, Regeneron Pharmaceuticals Inc, Tarrytown, New York
  • N. Gale
    Ophthalmology, Regeneron Pharmaceuticals Inc, Tarrytown, New York
  • J. S. Rudge
    Ophthalmology, Regeneron Pharmaceuticals Inc, Tarrytown, New York
  • G. D. Yancopoulos
    Ophthalmology, Regeneron Pharmaceuticals Inc, Tarrytown, New York
  • S. J. Wiegand
    Ophthalmology, Regeneron Pharmaceuticals Inc, Tarrytown, New York
  • Footnotes
    Commercial Relationships J. Cao, Regeneron Pharmaceuticals Inc, E; Y. Liu, Regeneron Pharmaceuticals Inc, E; N. Gale, Regeneron Pharmaceuticals Inc, E; J.S. Rudge, Regeneron Pharmaceuticals Inc, E; G.D. Yancopoulos, Regeneron Pharmaceuticals Inc, E; S.J. Wiegand, Regeneron Pharmaceuticals Inc, E.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3198. doi:https://doi.org/
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    • Get Citation

      J. Cao, Y. Liu, N. Gale, J. S. Rudge, G. D. Yancopoulos, S. J. Wiegand; Genetic Deletion or Pharmacological Inhibition of Angiopoietin-2 Reduces Injury-Induced Corneal Neovascularization, Lymphangiogenesis and Inflammation. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3198. doi: https://doi.org/.

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

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Abstract

Purpose:: To evaluate the role of endogenous Angiopoietin-2 (Ang2) in the development of corneal neovascularization and inflammation.

Methods:: Adult mice (7-14 weeks of age) homozygous for Ang2 deletion / LacZ substitution (Ang2-/-), their wild type (WT) littermates, and adult male C57Bl/6 mice were used in these studies. Corneal neovascularization (NV) was induced by intrastromal placement of 3 nylon sutures in the right eye (day 0). In C57Bl/6 mice, a neutralizing Ang2 antibody (25mg/kg) or a control protein (human Fc, 10mg/kg) was injected subcutaneously on days 0, 3 and 6 following corneal injury. On day 9 after corneal injury, the vasculature was labeled by intravenous injection of fluorescein conjugated lectin (lycopersicon esculentum), and corneal NV was evaluated in flat-mounts. Lymphatic vessels were co-localized in the same specimens by LYVE-1 immunostaining. Macrophage infiltration was evaluated in cross-sections stained with rat anti-mouse F4/80 monoclonal antibody. The Scion Image program was used for analysis of the area and length of corneal neovessels. Corneal thickness also was measured in cross-sections, as an index of edema.

Results:: The vasculature at the corneal limbus exhibited abnormalities in adult Ang2-/- mice, most notably a reduction in the caliber of the major circumferential veins and arteries. Following suture injury, corneal NV was significantly reduced in the Ang2-/- mice compared to their WT littermates (p <0.001) and also altered qualitatively, with the neovessels being much finer in the Ang2-/- mice. Genetic deletion of Ang2 also dramatically reduced the infiltration of macrophages into the damaged cornea. Systemic treatment with Ang2 antibody significantly inhibited corneal NV (p < 0.001) in C57Bl.6 mice. Ang2 antibody treatment also markedly decreased the growth of lymphatic vessels into the injured cornea and reduced corneal edema.

Conclusions:: These findings demonstrate that endogenous Ang2 plays an important role in the development of neovascularization, lymphangiogenesis and inflammation following corneal injury.

Keywords: growth factors/growth factor receptors • neovascularization • inflammation 
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