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

Kaufman Lab // Publications // Jul 01 2000

PubMed ID: 10900110

Author(s): Sabanay I, Gabelt BT, Tian B, Kaufman PL, Geiger B. H-7 effects on the structure and fluid conductance of monkey trabecular meshwork. Arch Ophthalmol. 2000 Jul;118(7):955-62. PMID 10900110

Journal: Archives Of Ophthalmology (Chicago, Ill. : 1960), Volume 118, Issue 7, Jul 2000

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. Arch Ophthalmol. 2000;118:955-962