 |
|
H-7 Effects on the Structure and Fluid Conductance of Monkey Trabecular Meshwork
Ilana Sabanay, PhD;
B'Ann T. Gabelt, MS;
Baohe Tian, MD;
Paul L. Kaufman, MD;
Benjamin Geiger, PhD
Arch Ophthalmol. 2000;118:955-962.
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.
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.
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Reduction of the Available Area for Aqueous Humor Outflow and Increase in Meshwork Herniations into Collector Channels Following Acute IOP Elevation in Bovine Eyes
Battista et al.
IOVS 2008;49:5346-5352.
ABSTRACT
| FULL TEXT
Specialized Podosome- or Invadopodia-like Structures (PILS) for Focal Trabecular Meshwork Extracellular Matrix Turnover
Aga et al.
IOVS 2008;49:5353-5365.
ABSTRACT
| FULL TEXT
Bone Morphogenetic Protein-7 Is an Antagonist of Transforming Growth Factor-{beta}2 in Human Trabecular Meshwork Cells
Fuchshofer et al.
IOVS 2007;48:715-726.
ABSTRACT
| FULL TEXT
Aqueous humor outflow: what do we know? Where will it lead us?
Fautsch et al.
IOVS 2006;47:4181-4187.
FULL TEXT
Research Opportunities in Vision: A Report of the U.S.-Indo Workshops on Collaborative Research
Balasubramanian et al.
IOVS 2006;47:1717-1735.
FULL TEXT
Cationic Ferritin and Segmental Flow through the Trabecular Meshwork
Hann et al.
IOVS 2005;46:1-7.
ABSTRACT
| FULL TEXT
Biomechanics of Schlemm's Canal Endothelial Cells: Influence on F-Actin Architecture
Ethier et al.
Biophys. J 2004;87:2828-2837.
ABSTRACT
| FULL TEXT
Effect of Low-Dose Latrunculin B on Anterior Segment Physiologic Features in the Monkey Eye
Okka et al.
Arch Ophthalmol 2004;122:1482-1488.
ABSTRACT
| FULL TEXT
H-7 Effect on Outflow Facility after Trabecular Obstruction Following Long-Term Echothiophate Treatment in Monkeys
Gabelt et al.
IOVS 2004;45:2732-2736.
ABSTRACT
| FULL TEXT
Effects of Topical H-7 on Outflow Facility, Intraocular Pressure, and Corneal Thickness in Monkeys
Tian et al.
Arch Ophthalmol 2004;122:1171-1177.
ABSTRACT
| FULL TEXT
Effect of Heparin II Domain of Fibronectin on Aqueous Outflow in Cultured Anterior Segments of Human Eyes
Santas et al.
IOVS 2003;44:4796-4804.
ABSTRACT
| FULL TEXT
The Mechanism of Increasing Outflow Facility during Washout in the Bovine Eye
Overby et al.
IOVS 2002;43:3455-3464.
ABSTRACT
| FULL TEXT
Signaling Mechanism of TGF-{beta}1-Induced Collagen Contraction Mediated by Bovine Trabecular Meshwork Cells
Nakamura et al.
IOVS 2002;43:3465-3472.
ABSTRACT
| FULL TEXT
|
