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(Investigative Ophthalmology and Visual Science. 2000;41:1749-1758.)
© 2000 by The Association for Research in Vision and Ophthalmology, Inc.

Latrunculins’ Effects on Intraocular Pressure, Aqueous Humor Flow, and Corneal Endothelium

Jennifer A. Peterson1, Baohe Tian1, Jay W. McLaren2, William C. Hubbard1, Benjamin Geiger3 and Paul L. Kaufman1

1 From the Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison; the 2 Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota; and the 3 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

PURPOSE. To determine the effects of latrunculin (LAT)-A or -B on intraocular pressure (IOP), aqueous humor flow (AHF), anterior chamber (AC) protein concentration ([protein]AC), corneal endothelial permeability and morphology, and corneal thickness in living cynomolgus monkeys.

METHODS. Topical LAT-A or LAT-B was administered to one eye, and vehicle to the other. IOP was measured by Goldmann tonometry, AHF and corneal endothelium transfer coefficient (ka) by fluorophotometry, [protein]AC by Lowry assay, corneal endothelial cell morphology by specular microphotography, and corneal thickness by ultrasound pachymetry.

RESULTS. LAT-A began to lower IOP at 6 hours and maximally reduced IOP by 4.6 mm Hg at 9 hours. LAT-B lowered IOP within 1 hour and maximally reduced IOP by 3.1 mm Hg at 6 hours. LAT-A increased AHF by 87% for 3 hours and increased ka by 94% over 6 hours; LAT-B increased ka by 39% over 6 hours without affecting AHF. LAT-A increased IV fluorescein entry into the cornea approximately 10 fold, but did not affect IV fluorescein entry into the AC. LAT-A increased [protein]AC by 25% at 2 hours but not 5.5 hours. LAT-B variably and insignificantly increased [protein]AC at 1 hour but not at 6.5 hours. LAT-A induced extensive corneal endothelial pseudoguttata within 1 hour, with normal cell counts by 7 days. LAT-B increased central corneal thickness maximally by 47 µm at 3.5 hours.

CONCLUSIONS. LAT-A and -B significantly reduced IOP and were consistent in their facility-increasing effect, indicating that pharmacologic disorganization of the actin cytoskeleton in the trabecular meshwork by latrunculins may be a useful antiglaucoma strategy. However, effects on corneal endothelium or ciliary epithelium are a potential safety issue.




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