H-1152 effects on intraocular pressure and trabecular meshwork morphology of rat eyes.

Brandt Lab // Kaufman Lab // Publications // Jul 31 2008

PubMed ID: 18665808

Author(s): Yu M, Chen X, Wang N, Cai S, Li N, Qiu J, Brandt CR, Kaufman PL, Liu X. H-1152 effects on intraocular pressure and trabecular meshwork morphology of rat eyes. J Ocul Pharmacol Ther. 2008 Aug;24(4):373-9. doi: 10.1089/jop.2008.0029.

Journal: Journal Of Ocular Pharmacology And Therapeutics : The Official Journal Of The Association For Ocular Pharmacology And Therapeutics, Volume 24, Issue 4, Aug 2008

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 microM 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.