Inhibition of Corneal Neovascularization by Subconjunctival Injection of Fc-Endostatin, a Novel Inhibitor of Angiogenesis.
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.
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Junko
J
Yoshida
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Robert T
RT
Wicks
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Andrea I
AI
Zambrano
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Betty M
BM
Tyler
Center of Cancer Systems Biology, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA.
Kashi
K
Javaherian
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Rachel
R
Grossman
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Yassine J
YJ
Daoud
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Peter
P
Gehlbach
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.
Henry
H
Brem
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Walter J
WJ
Stark