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-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.


CONCLUSIONS
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.


CONCLUSIONS
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
Sabanay
I
I
Department of Ophthalmology and Visual Sciences, University of Wisconsin Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3220, USA.
Gabelt
B T
BT
Tian
B
B
Kaufman
P L
PL
Geiger
B
B
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology*; D000818:Animals; D000867:Anterior Chamber / Q000378:metabolism; D001082:Aqueous Humor / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017979:Gold Colloid / Q000378:metabolism; D007429:Intraocular Pressure / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D017979:Gold Colloid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017346:Protein Serine-Threonine Kinases