H-7 effects on the structure and fluid conductance of monkey trabecular meshwork

Objective: To determine the effects of H-7 (1-[5-isoquinoline sulfonyl]-2-m ethyl piperazine) on the structure and fluid conductance of the trabecular meshwork of live cynomolgus monkeys. Methods: Fluid outflow was measured by constart pressure perfusion of the a nterior chamber with cationized and noncationized gold solution with or wit hout H-7 in opposite eyes. The eyes were fixed by infusing Ito solution and enucleated. Anterior segments were cut Into 4 sections, fixed in immersion solution, and embedded in epoxy resin-812. Trabecular meshwork morphologic features were studied by light and electron microscopy. Results: H-7 affected trabecular meshwork organization and increased fluid outflow. H-7 expanded the intercellular spaces in the juxtacanalicular mesh work, accompanied by removal of extracellular material. The inner wall cell s of the Schlemm canal became highly extended, yet cell-cell junctions were maintained. Colloidal gold particles were detected only in limited areas a long the subcanalicular region in control eyes; after H-7 treatment, gold w as widely seen along, the entire inner canal wall. Most inner wall cells in H-7-treated eyes, but only few cells in control eyes, contained gold-loade d vesicles. Conclusion: H-7 inhibits cell contractility leading to " relaxation " of th e trabecular outflow pathway, expanding the draining surface, and permittin g more extensive flow through the meshwork. Clinical Relevance: By inhibiting cellular contractility and relaxing the t rabecular meshwork, the protein kinase inhibitor H-7 increases outflow faci lity and reduces intraocular pressure and thus has potential as an ocular h ypotensive antiglaucoma medication.