The Effect of the Rho-Associated Protein Kinase Inhibitor, HA-1077, in the Rabbit Ocular Hypertension Model Induced by Water Loading

• Published in: Current eye research 2009, Vol.34 (1), p.42-47
• Main Authors: Fukunaga, Takaki, Ikesugi, Kengo, Nishio, Masahiro, Sugimoto, Masahiko, Sasoh, Mikio, Hidaka, Hiroyoshi, Uji, Yukitaka
• Format: Article
• Language: English
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - administration & dosage; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - adverse effects; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; Administration, Topical; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; intraocular pressure (IOP); Intraocular Pressure - drug effects; Male; Ocular Hypertension - drug therapy; Ophthalmic Solutions - administration & dosage; Ophthalmic Solutions - adverse effects; Ophthalmic Solutions - pharmacology; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - pharmacology; Rabbits; rho-Associated Kinases - antagonists & inhibitors; Rho-associated protein kinase (ROCK); ROCK inhibitor HA-1077; Stress, Physiological; Time Factors; trabecular meshwork; Water; water loading
• ISSN: 0271-3683; 1460-2202
• DOI: 10.1080/02713680802531353

Purpose: The aim of this study was to investigate the intraocular pressure (IOP)-lowering effect of a new anti-glaucoma drug, the Rho-associated protein kinase (ROCK) inhibitor, HA-1077, in a rabbit ocular hypertension model. Methods: Experiments were carried out in 18 male New Zealand white rabbits, with ocular hypertension induced by water loading. Animals were divided into three groups followed by topical administration of 1 mM, 2 mM, and 3 mM HA-1077 in the left eye. As a control, phosphate buffered saline was administered in the opposite eye. Results: After administration of HA-1077 eye drops, there was a significant time- and dose-dependent decrease of the IOP. While minor conjunctival injection was seen in a few cases, no abnormalities of the anterior chamber or fundus were observed. Conclusions: This is the first report of the effect of the ROCK inhibitor, HA-1077, on the IOP in an ocular hypertension model. Study results indicated that HA-1077 has a strong IOP-lowering effect.