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Jennifer A. Peterson, Baohe Tian, Jay W. McLaren, William C. Hubbard, Benjamin Geiger, Paul L. Kaufman; Latrunculins’ Effects on Intraocular Pressure, Aqueous Humor Flow, and Corneal Endothelium. Invest. Ophthalmol. Vis. Sci. 2000;41(7):1749-1758.
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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
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 (k a) 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 k a by 94% over 6 hours; LAT-B
increased k a 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
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