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Abstract #6517 Published in IGR 3-2
Effects of protein kinase inhibitor, HA1077, on intraocular pressure and outflow facility in rabbit eyes
Honjo M; Inatani M; Kido N; Sawamura T; Yue BYJT; Honda Y; Tanihara HArchives of Ophthalmology 2001; 119: 1171-1178
OBJECTIVE: To elucidate the roles of protein kinase in regulating the intraocular pressure (IOP) and outflow facility in rabbit eyes. MATERIALS AND METHODS: A protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-homopiperazine (HA1077), was used. IOP and outflow facility were measured before and after topical, intracameral, or intravitreal administration of HA1077 in rabbits. Western blot analysis was performed to detect the 20-kd light chain of myosin in human trabecular meshwork (TM) cells and bovine ciliary muscle (CM) tissues. The cell morphological condition and distribution of actin filaments and vinculin in TM cells were studied using cell biology techniques. Carbachol-induced contraction of isolated bovine CM strips following administration of HA1077 was examined in a perfusion chamber. RESULTS: In rabbit eyes, the administration of HA1077 resulted in a significant decrease of IOP in a dose-dependent manner. An increased outflow facility was also observed. Western blot analysis revealed the presence of 20-kd light chain of myosin in human TM cells, and bovine CM tissues. In cultured human TM cells, exposure to HA1077 disrupted actin bundles and impaired focal adhesion formation. In addition, HA1077 showed relaxation of bovine CM strips. CONCLUSIONS: use of HA1077 caused a reduction in IOP and an increase in the outflow facility. The results of in vitro experiments suggest that the IOP-lowering effects of HA1077 may be related to the altered cellular behavior of TM cells and relaxation of CM contraction. The results of these studies suggested that protein kinase inhibitors have the potential to be developed into a treatment modality for glaucoma.
Dr M. Honjo, Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
