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 fr...

Full description

Saved in:
Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Journal of Ophthalmology
Online Access:http://dx.doi.org/10.1155/2015/137136
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832554808857329664
author 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
author_facet 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
author_sort Junko Yoshida
collection DOAJ
description 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.
format Article
id doaj-art-92dd39d85f344968bbe79b149433da1f
institution Kabale University
issn 2090-004X
2090-0058
language English
publishDate 2015-01-01
publisher Wiley
record_format Article
series Journal of Ophthalmology
spelling doaj-art-92dd39d85f344968bbe79b149433da1f2025-02-03T05:50:28ZengWileyJournal of Ophthalmology2090-004X2090-00582015-01-01201510.1155/2015/137136137136Inhibition of Corneal Neovascularization by Subconjunctival Injection of Fc-Endostatin, a Novel Inhibitor of AngiogenesisJunko Yoshida0Robert T. Wicks1Andrea I. Zambrano2Betty M. Tyler3Kashi Javaherian4Rachel Grossman5Yassine J. Daoud6Peter Gehlbach7Henry Brem8Walter J. Stark9Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USAWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USADepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USACenter of Cancer Systems Biology, St. Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, MA 02111, USADepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USAWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USAWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USAWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USAWilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USAWe 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.http://dx.doi.org/10.1155/2015/137136
spellingShingle 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
Inhibition of Corneal Neovascularization by Subconjunctival Injection of Fc-Endostatin, a Novel Inhibitor of Angiogenesis
Journal of Ophthalmology
title Inhibition of Corneal Neovascularization by Subconjunctival Injection of Fc-Endostatin, a Novel Inhibitor of Angiogenesis
title_full Inhibition of Corneal Neovascularization by Subconjunctival Injection of Fc-Endostatin, a Novel Inhibitor of Angiogenesis
title_fullStr Inhibition of Corneal Neovascularization by Subconjunctival Injection of Fc-Endostatin, a Novel Inhibitor of Angiogenesis
title_full_unstemmed Inhibition of Corneal Neovascularization by Subconjunctival Injection of Fc-Endostatin, a Novel Inhibitor of Angiogenesis
title_short Inhibition of Corneal Neovascularization by Subconjunctival Injection of Fc-Endostatin, a Novel Inhibitor of Angiogenesis
title_sort inhibition of corneal neovascularization by subconjunctival injection of fc endostatin a novel inhibitor of angiogenesis
url http://dx.doi.org/10.1155/2015/137136
work_keys_str_mv AT junkoyoshida inhibitionofcornealneovascularizationbysubconjunctivalinjectionoffcendostatinanovelinhibitorofangiogenesis
AT roberttwicks inhibitionofcornealneovascularizationbysubconjunctivalinjectionoffcendostatinanovelinhibitorofangiogenesis
AT andreaizambrano inhibitionofcornealneovascularizationbysubconjunctivalinjectionoffcendostatinanovelinhibitorofangiogenesis
AT bettymtyler inhibitionofcornealneovascularizationbysubconjunctivalinjectionoffcendostatinanovelinhibitorofangiogenesis
AT kashijavaherian inhibitionofcornealneovascularizationbysubconjunctivalinjectionoffcendostatinanovelinhibitorofangiogenesis
AT rachelgrossman inhibitionofcornealneovascularizationbysubconjunctivalinjectionoffcendostatinanovelinhibitorofangiogenesis
AT yassinejdaoud inhibitionofcornealneovascularizationbysubconjunctivalinjectionoffcendostatinanovelinhibitorofangiogenesis
AT petergehlbach inhibitionofcornealneovascularizationbysubconjunctivalinjectionoffcendostatinanovelinhibitorofangiogenesis
AT henrybrem inhibitionofcornealneovascularizationbysubconjunctivalinjectionoffcendostatinanovelinhibitorofangiogenesis
AT walterjstark inhibitionofcornealneovascularizationbysubconjunctivalinjectionoffcendostatinanovelinhibitorofangiogenesis