April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Inhibition Of Angiogenesis By Fc-endostatin
Robert T. Wicks; Junko Yoshida; Andrea Zambrano; Betty Tyler; Kashi Javaherian; Peter Gehlbach; Yassine J. Daoud; Henry Brem; Walter J. Stark
Author Affiliations & Notes
  • Robert T. Wicks
    Wilmer Eye Institute,
    Johns Hopkins University SOM, Baltimore, Maryland
  • Junko Yoshida
    Wilmer Eye Institute,
    Johns Hopkins University SOM, Baltimore, Maryland
  • Andrea Zambrano
    Wilmer Eye Institute,
    Johns Hopkins University SOM, Baltimore, Maryland
  • Betty Tyler
    Dept. of Neurosurgery,
    Johns Hopkins University SOM, Baltimore, Maryland
  • Kashi Javaherian
    Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts
  • Peter Gehlbach
    Wilmer Eye Institute,
    Johns Hopkins University SOM, Baltimore, Maryland
  • Yassine J. Daoud
    Wilmer Eye Institute,
    Johns Hopkins University SOM, Baltimore, Maryland
  • Henry Brem
    Dept. of Neurosurgery,
    Johns Hopkins University SOM, Baltimore, Maryland
  • Walter J. Stark
    Wilmer Eye Institute,
    Johns Hopkins University SOM, Baltimore, Maryland
  • Footnotes
    Commercial Relationships  Robert T. Wicks, None; Junko Yoshida, None; Andrea Zambrano, None; Betty Tyler, None; Kashi Javaherian, None; Peter Gehlbach, None; Yassine J. Daoud, None; Henry Brem, None; Walter J. Stark, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 6694. doi:
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      Robert T. Wicks, Junko Yoshida, Andrea Zambrano, Betty Tyler, Kashi Javaherian, Peter Gehlbach, Yassine J. Daoud, Henry Brem, Walter J. Stark; Inhibition Of Angiogenesis By Fc-endostatin. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6694.

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Abstract

Purpose: : Endostatin is a potent angiogenic inhibitor with a brief, 2 hour half-life. Fc-endostatin (FcE) is a recombinant form of human endostatin bound to the Fc domain of IgG antibody, which increases its half-life to several weeks. We assessed the antiangiogenic effect of subconjunctival injected FcE compared to bevacizumab (Avastin®) (BV), using a rabbit VEGF-induced corneal neovascularization, micropocket assay.

Methods: : Neovascularization was induced in rabbit corneas through intrastromal implantation of VEGF polymer at 6 and 12 o’clock, 2mm from the limbus. A total of 32 pellets were placed in the 16 eyes of 8 adult rabbits. Rabbits were randomized to 4 treatment groups, each receiving subconjunctival injections in both eyes on Days 0, 5, 8, and 12 of: 1) 0.1mL saline, 2) 0.1mL BV 25mg/mL, 3) 0.125mL FcE 2mg/mL (FcE 2), or 4) 0.125mL of FcE 20mg/mL (FcE 20). Corneas were digitally-imaged on Days 0, 5, 8, 12, and 15. An angiogenesis index (AI) was calculated [vessel length (mm) x vessel number] for each polymer observation.

Results: : All treatment groups showed a significant decrease in the AI compared to saline on all observation days (p<0.001). FcE 2 decreased angiogenesis by a factor of 8.1, 7.0, 8.8, and 6.8 on Days 5, 8, 12, and 15, respectively. FcE 20 decreased angiogenesis by a factor of 68, 2.7, 3.6, and 2.4 at 5, 8, 12, and 15 days. BV, the positive control, decreased VEGF-induced angiogenesis compared to saline by a factor of 138 on Day 15, with no vessel growth at 5, 8, and 12 days. BV was a significantly better inhibitor than FcE 20 by Day 8 (p<0.01). By Day 15, FcE 2 inhibited angiogenesis significantly better than FcE 20 (p<0.01).

Conclusions: : FcE at both 2mg/mL and 20mg/mL doses significantly inhibited angiogenesis. Lower concentration FcE 2 exhibited better inhibition of vessel growth than FcE 20. These results are consistent with previous FcE studies referencing a biphasic dose-response curve. FcE 20 was found to be a less potent VEGF inhibitor than BV. FcE should be further investigated as a novel therapy for corneal neovascularization.

Keywords: neovascularization • cornea: basic science 
© 2011, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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