Lack of association between VAP-1/SSAO activity and corneal neovascularization in a rabbit model.

Abstract

The aim of this study is to determine the efficacy of a potent and specific vascular adhesive protein-1/semicarbazide-sensitive amine oxidase (VAP-1/SSAO) inhibitor, LJP 1207, as a potential antiangiogenic and anti-inflammatory agent in the therapy of corneal neovascularization. Corneal neovascularization was induced with intrastromal suturing in rabbits (n = 20). Topical treatment with VAP-1/SSAO inhibitor LJP 1207 (n = 5, 4 times a day), bevacizumab (n = 5, daily), their combination (n = 5) and vehicle only (n = 5, 4 times a day) were applied postoperatively for 2 weeks. The development and extent of corneal neovascularization were evaluated by digital image analysis. At the end of the observation period, the level of corneal and serum VAP-1/SSAO activity was measured fluorometrically and radiochemically. The corneal VAP-1/SSAO activity was significantly elevated in the suture-challenged vehicle-treated group (3,075 ± 1,009 pmol/mg/h) as compared to unoperated controls (464.2 ± 135 pmol/mg/h, p < 0.001). Treatment with LJP 1207 resulted in slower early phase neovascularization compared to vehicle-treated animals (not significant). At days 7-14, there was no significant difference in the extent of corneal neovascularization between inhibitor- and vehicle-treated corneas, even though inhibitor treatment caused a normalization of corneal VAP-1/SSAO activity (885 ± 452 pmol/mg/h). Our results demonstrate that the significant elevation of VAP-1/SSAO activity due to corneal injury can be prevented with VAP-1/SSAO inhibitor LJP 1207 treatment. However, normalization of VAP-1/SSAO activity in this model does not prevent the development of corneal neovascularization.

• Authors: Anna Énzsöly, Katalin Markó, Tamás Tábi, Éva Szökő, Romána Zelkó, Miklós Tóth, J Mark Petrash, Péter Mátyus, János Németh
• Journal: Journal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 120 Issue 6 Pg. 969-75 (Jun 2013) ISSN: 1435-1463 [Electronic] Austria
• PMID: 23397320 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Anti-Inflammatory Agents
• Antibodies, Monoclonal, Humanized
• Hydrazines
• N'-(2-phenylallyl)hydrazine
• Bevacizumab
• Amine Oxidase (Copper-Containing)

Topics

• Amine Oxidase (Copper-Containing) (metabolism)
• Angiogenesis Inhibitors (therapeutic use)
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Bevacizumab
• Cornea (enzymology)
• Corneal Neovascularization (blood, drug therapy, etiology, metabolism)
• Disease Models, Animal
• Drug Interactions
• Hydrazines (blood, therapeutic use)
• Male
• Rabbits
• Suture Techniques (adverse effects)
• Time Factors