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

J Neural Transm (Vienna). 2013 Jun;120(6):969-75. doi: 10.1007/s00702-013-0986-0. Epub 2013 Feb 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Corneal Neovascularization / drug therapy
  • Corneal Neovascularization / etiology
  • Corneal Neovascularization / metabolism*
  • Disease Models, Animal
  • Drug Interactions
  • Hydrazines / blood
  • Hydrazines / therapeutic use
  • Male
  • Rabbits
  • Suture Techniques / adverse effects
  • Time Factors

Substances

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