title: 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: Department of Ophthalmology, Semmelweis University, Tomo u. 25-29, Budapest, 1083, Hungary. enzsoly.anna@med.semmelweis-univ.hu
authors: Anna
authors: A
authors: Énzsöly
authors: Katalin
authors: K
authors: Markó
authors: Tamás
authors: T
authors: Tábi
authors: Éva
authors: É
authors: Szökő
authors: Romána
authors: R
authors: Zelkó
authors: Miklós
authors: M
authors: Tóth
authors: J Mark
authors: JM
authors: Petrash
authors: Péter
authors: P
authors: Mátyus
authors: János
authors: J
authors: Németh
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D003315:Cornea / Q000201:enzymology*; D016510:Corneal Neovascularization / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D004195:Disease Models, Animal; D004347:Drug Interactions; D006834:Hydrazines / Q000097:blood / Q000627:therapeutic use; D008297:Male; D011817:Rabbits; D013536:Suture Techniques / Q000009:adverse effects; D013997:Time Factors
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D006834:Hydrazines; C506836:N'-(2-phenylallyl)hydrazine; D000068258:Bevacizumab; D006631:Amine Oxidase (Copper-Containing)
references: Curr Med Chem. 2008;15(18):1827-39
references: 18691041
references: Med Sci Monit. 2005 Apr;11(4):RA122-6
references: 15795708
references: Exp Eye Res. 2010 Jan;90(1):26-32
references: 19761765
references: Diabetes. 1993 Apr;42(4):594-603
references: 8454111
references: J Pharmacol Exp Ther. 2005 Nov;315(2):553-62
references: 16081681
references: Prog Retin Eye Res. 2007 Jan;26(1):1-37
references: 17074526
references: Circ Res. 2004 Jul 9;95(1):50-7
references: 15178639
references: FASEB J. 2008 Aug;22(8):2928-35
references: 18436961
references: Anal Biochem. 1976 May 7;72:248-54
references: 942051
references: Anal Biochem. 1997 Nov 15;253(2):169-74
references: 9367499
references: Cornea. 2012 Mar;31(3):322-34
references: 22157572
references: Cardiovasc Toxicol. 2002;2(2):141-50
references: 12271157
references: Curr Opin Ophthalmol. 2001 Aug;12(4):242-9
references: 11507336
references: J Neural Transm (Vienna). 2011 Jul;118(7):1065-9
references: 21331460
references: Brain Res Bull. 2010 Feb 15;81(2-3):198-210
references: 19481138
references: J Pharmacol Exp Ther. 2006 Apr;317(1):19-29
references: 16339390
references: Neurotoxicology. 2004 Jan;25(1-2):303-15
references: 14697905
references: Cornea. 2011 Aug;30(8):927-38
references: 21389854
references: Arterioscler Thromb Vasc Biol. 2008 Jan;28(1):18-26
references: 17962625
references: Life Sci. 2011 Feb 14;88(7-8):302-6
references: 21146547
references: Ophthalmologe. 2009 May;106(5):399-406
references: 19396447
references: Cornea. 2012 Aug;31(8):937-44
references: 22357391
references: Med Oncol. 2004;21(3):241-50
references: 15456951
references: J Neural Transm (Vienna). 2007;114(6):845-9
references: 17393060