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Abstract #6216 Published in IGR 2-2
Latrunculins' effects on intraocular pressure, aqueous humor flow, and corneal endothelium
Peterson JA; Tian B; McLaren JW; Hubbard WC; Geiger B; Kaufman PLInvestigative Ophthalmology and Visual Science 2000; 41: 1749-1758
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 six hours and maximally reduced IOP by 4.6 mmHg at nine hours. LAT-B lowered IOP within one hour and maximally reduced IOP by 3.1 mmHg at six hours. LAT-A increased AHF by 87% for three hours and increased ka by 94% over six hours; LAT-B increased ka by 39% over six hours without affecting AHF. LAT-A increased IV fluorescein entry into the cornea approximately ten-fold, but did not affect IV fluorescein entry into the AC. LAT-A increased (protein)AC by 25% at two hours but not at 5.5 hours. LAT-B variably and insignificantly increased (protein)AC: at one hour but not at 6.5 hours. LAT-A induced extensive corneal endothelial pseudoguttata within one hour, with normal cell counts by seven 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 pharmacological 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.
Dr. J. A. Peterson, Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
