Effect Of H-1152 On Intraocular Pressure Rabbits

Purpose To determine the effects of Rho-kinase inhibitor H-1152 on intraocular pressure (IOP) of rabbit eyes and on cultured human trabecular meshwork (HTM) cells.Methods The IOP was measured before and after the topical administration of H-1152 (10mM) on rabbit eyes. Transmission electron microscopy was used to identify changes in rabbit trabecular meshwork (TM). Cultured human trabecular meshwork (HTM) cells were treated with H-1152 (20μM), and the changes in morphology and distribution of actin and vinculin were determined.Results In rabbit eyes, H-1152 resulted in a significant decrease in IOP (n=6, p<0.05), and no obvious side effects were detected. In cultured HTM cells, H-1152 induced changes in cell shape include cell rounding up and retraction. H-1152 also induced disruption of actin and reduced vinculin-positive focal adhesions. However, recovery of morphology and organization of actin and vinculin were documented 24 hours after withdrawing H-1152. There were no obvious changes of TM in organization under light microscope. Results of transmission electron microscopy showed widening of the extracellular spaces between the beams in rabbit trabecular meshwork.Conclusion H-1152 is able to lower rabbit IOP and disrupt or reorganize formation of actin cystoskeleton, cell– cell adhesions and cell–ECM adhesions by inhibiting activity of Rho-kinase. Therefore, it can be a potential novel antiglaucoma medication.