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Abstract #11439 Published in IGR 6-3
Effect of low-dose latrunculin B on anterior segment physiologic features in themonkey eye
Okka M; Tian B; Kaufman PLArchives of Ophthalmology 2004; 122: 1482-1488
OBJECTIVES: To determine if low doses of topical latrunculin B (LAT-B) will increase outflow facility and decrease intraocular pressure without damaging the cornea and if they will inhibit miotic and accommodative responses to pilocarpine in monkeys. METHODS: We measured intraocular pressure (Goldmann tonometry) before and after 1 and 9 doses of 0.005% and 0.01% topical LAT-B and vehicle given twice daily on successive weeks; outflow facility (perfusion) following 15 doses; central corneal thickness (ultrasonic pachymetry) before and after 1 and 9 doses of 0.01% LAT-B and vehicle; pupillary diameter (calipers); and accommodation (refractometry) before and after 1 dose of 0.005% and 0.02% LAT-B. RESULTS: Latrunculin-B dose-dependently decreased intraocular pressure, multiple doses more than a single dose. Maximal mean ± SEM hypotension after 1 dose was 2.5 ± 0.3 mmHg (0.005% LAT-B; n = 8; P<.001) or 2.7 ± 0.6 mmHg (0.01% LAT-B; n = 8; P<.005); maximal mean ± SEM hypotension after 9 doses was 3.2 ± 0.5 mmHg (0.005% LAT-B; n = 8; P<.001) or 4.4 ± 0.6 mmHg (0.01% LAT-B; n = 8; P<.001). Outflow facility was increased by mean ± SEM 75% ± 13% (n = 7; P<.005). Central corneal thickness was not changed after 1 or 9 doses of 0.01% LAT-B. Miotic and accommodative responses to intramuscular pilocarpine were dose-dependently inhibited. With 0.02% LAT-B, inhibition of miosis was substantial, whereas the inhibition of accommodation was only about 25%. With 0.005% LAT-B, the effects were trivial. CONCLUSIONS: In ocular normotensive monkeys, 0.005% and 0.01% LAT-B administered topically increases outflow facility and/or decreases intraocular pressure without corneal effects. Multiple doses reduce intraocular pressure more than a single dose. Latrunculin-B dose-dependently relaxes the iris sphincter and ciliary muscle, with some separation of miotic and accommodative effects. CLINICAL RELEVANCE: Multiple treatments with low topical doses of LAT-B may substantially reduce outflow resistance in eyes with glaucoma without adversely affecting the cornea.
Dr. M. Okka, Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison Medical School, 53792-3284, USA
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)