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...
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2015-01-01
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Series: | Journal of Ophthalmology |
Online Access: | http://dx.doi.org/10.1155/2015/137136 |
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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 |
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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 |
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