Inhibition of Corneal Neovascularization by Subconjunctival Injection of Fc-Endostatin, a Novel Inhibitor of Angiogenesis

Junko Yoshida, Robert T. Wicks, Andrea I. Zambrano, Betty M. Tyler, Kashi Javaherian, Rachel Grossman, Yassine J. Daoud, Peter Gehlbach, Henry Brem, Walter J. Stark

Research output: Contribution to journalArticle

Abstract

We assessed the antiangiogenic effects of subconjunctival injection of Fc-endostatin (FcE) using a human vascular endothelial growth factor-induced rabbit corneal neovascularization model. Angiogenesis was induced in rabbit corneas through intrastromal implantations of VEGF polymer implanted 2 mm from the limbus. NZW rabbits were separated into groups receiving twice weekly subconjunctival injections of either saline; 25 mg/mL bevacizumab; 2 mg/mL FcE; or 20 mg/mL FcE. Corneas were digitally imaged at 5 time points. An angiogenesis index (AI) was calculated (vessel length (mm) × vessel number score) for each observation. All treatment groups showed a significant decrease in the vessel length and AI compared to saline on all observation days (P<0.001). By day 15, FcE 2 inhibited angiogenesis significantly better than FcE 20 (P<0.01). There was no significant difference between FcE 2 and BV, although the values trended towards significantly increased inhibition by BV. BV was a significantly better inhibitor than FcE 20 by day 8 (P<0.01). FcE was safe and significantly inhibited new vessel growth in a rabbit corneal neovascularization model. Lower concentration FcE 2 exhibited better inhibition than FcE 20, consistent with previous FcE studies referencing a biphasic dose-response curve. Additional studies are necessary to further elucidate the efficacy and clinical potential of this novel angiogenesis inhibitor.

Original languageEnglish (US)
Article number137136
JournalJournal of Ophthalmology
Volume2015
DOIs
StatePublished - Jan 1 2015

ASJC Scopus subject areas

  • Ophthalmology

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