H-7 Effects on the Structure and Fluid Conductance of Monkey Trabecular Meshwork | Glaucoma | JAMA Ophthalmology | JAMA Network
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Laboratory Sciences
July 2000

H-7 Effects on the Structure and Fluid Conductance of Monkey Trabecular Meshwork

Author Affiliations

From the Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel (Drs Sabanay and Geiger); and the Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison (Ms Gabelt and Drs Tian and Kaufman). The University of Wisconsin, Madison, and the Weizmann Institute of Science hold a patent related to this article; accordingly, Drs Kaufman and Geiger have a proprietary interest in the article. Alcon Laboratories, Inc, Fort Worth, Tex, has paid a fee to Drs Kaufman and Geiger for an option to license this technology and has provided some financial support in this general area. Dr Kaufman has also served as a paid consultant on unrelated issues for Alcon Laboratories, Inc, and several other pharmaceutical corporations.

Arch Ophthalmol. 2000;118(7):955-962. doi:10-1001/pubs.Ophthalmol.-ISSN-0003-9950-118-7-els90042

Objective  To determine the effects of H-7 (1-[5-isoquinoline sulfonyl]-2-methyl piperazine) on the structure and fluid conductance of the trabecular meshwork of live cynomolgus monkeys.

Methods  Fluid outflow was measured by constant pressure perfusion of the anterior chamber with cationized and noncationized gold solution with or without 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 meshwork, accompanied by removal of extracellular material. The inner wall cells of the Schlemm canal became highly extended, yet cell-cell junctions were maintained. Colloidal gold particles were detected only in limited areas along the subcanalicular region in control eyes; after H-7 treatment, gold was 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-loaded vesicles.

Conclusion  H-7 inhibits cell contractility, leading to "relaxation" of the trabecular outflow pathway, expanding the draining surface, and permitting more extensive flow through the meshwork.

Clinical Relevance  By inhibiting cellular contractility and relaxing the trabecular meshwork, the protein kinase inhibitor H-7 increases outflow facility and reduces intraocular pressure and thus has potential as an ocular hypotensive antiglaucoma medication.