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

doi:10.1155/2015/137136

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

J Ophthalmol. 2015:2015:137136. doi: 10.1155/2015/137136. Epub 2015 Sep 28.

Authors

Affiliations

¹ Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
² Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
³ Center of Cancer Systems Biology, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA.
⁴ Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA ; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA ; Departments of Oncology and Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

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.