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Abstract #22057 Published in IGR 10-4
H-1152 effects on intraocular pressure and trabecular meshwork morphology of rat eyes
Yu M; Chen X; Wang N; Cai S; Li N; Qiu J; Brandt CR; Kaufman PL; Liu XJournal of Ocular Pharmacology and Therapeutics 2008; 24: 373-379
PURPOSE: The aim of this study was to elucidate the effects of the Rho-kinase inhibitor, H-1152, on cultured human trabecular meshwork (HTM) cells, TM morphology, and intraocular pressure (IOP) in rats. METHODS: Cultured HTM cells were treated with H-1152. Changes in cell morphology and the organization of the actin cytoskeleton and focal adhesions were evaluated by microscopy and immunofluorescence. H-1152 was administered topically to the eyes of conscious rats, and IOP was measured with a commercially available tonometer before and after treatment. The eyes were enucleated 1 h after treatment, fixed, and processed for morphologic analysis by light and electron microscopy. RESULTS: Exposure of the cultured HTM cells to 20 μM of H-1152 induced elongation and separation of cells, deterioration, and loss of actin stress fibers and focal adhesions within 2 h. Topical administration of H-1152 resulted in a significant decrease in IOP from 0.5 to 6 h, with the maximum IOP reduction of 28.1% at 1 h post-treatment (P < 0.001; n = 10). H-1152 caused an expansion of the intercellular spaces and loss of extracellular material in the juxtacanalicular region of the TM in rat eyes. CONCLUSIONS: The IOP-lowering effect of H-1152 in rat eyes is likely due to changes in TM-cell morphology, the actin cytoskeleton, and cellular adhesions in the conventional outflow pathway. H-1152 has potential as a new antiglaucoma medication.
Dr. X. Liu, West China Eye Center and Ophthalmic Laboratories, West China Hospital, Sichuan University, 37 Guo Xue Road, Chengdu 610041, China. xliu1213@yahoo.com.cn
