| Purpose To investigate the effects of Rho- kinase inhibitor (S)- (+)- 2-methyl - 1 - [(4 - methyl - 5- isoquinolinyl) sulfonyl] homopiperazine (H-1152) on cultured human trabecular meshwork (HTM) cells and on intraocular pressure (IOP) in rabbit eyes.Materials and methods A specific Rho-kinase inhibitor H-1152 (20μM) was used. The cell morphology and distribution of actin filaments and vinculin in TM cells were studied by cell biology techniques. The IOP was determined before and after the topical administration of H-1152 (10mM) in rabbits. Transmission electron microscopy was used to identify changes in rabbit trabecular meshwork (TM) tissues. Results In cultured human TM cells, exposure to H-1152 led to significant but reversible changes in cell shape and the organization of actin and vinculin. The cell bodies were either partially retracted, rounded, or very elongated compared to without treatment. The cells also demonstrated disrupted actin cytoskeleton and reduced vinculin-positive focal adhesions. However, the H-1152 solution was removed afterward and replaced with plain DMEM containing 10% FBS. In all cases, recovery of normal morphology and organization of actin and vinculin were documented 24 hours later. In rabbit eyes, administration of H-1152 resulted in a significant decrease in IOP. Results of transmission electron microscopy showed widening of the extracellular spaces between the beams in rabbit trabecular meshwork.Conclusion Administration of H-1152 caused a reduction in IOP of rabbit eyes and decrease of extracellular matrix (ECM) between the beams. The in vitro experiments suggest H-1152 is effective in disrupting actin filaments and cellular adhesions in HTM cells. These studies suggest that Rho-kinase inhibitor H-1152 can increase aqueous outflow facility through trabecular meshwork. It may have great potential to be developed for treatment of glaucoma.
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