To determine if low doses of topical latrunculin B (LAT-B) will increaseoutflow facility and decrease intraocular pressure without damaging the corneaand if they will inhibit miotic and accommodative responses to pilocarpinein monkeys.
We measured intraocular pressure (Goldmann tonometry) before and after1 and 9 doses of 0.005% and 0.01% topical LAT-B and vehicle given twice dailyon successive weeks; outflow facility (perfusion) following 15 doses; centralcorneal thickness (ultrasonic pachymetry) before and after 1 and 9 doses of0.01% LAT-B and vehicle; pupillary diameter (calipers); and accommodation(refractometry) before and after 1 dose of 0.005% and 0.02% LAT-B.
Latrunculin-B dose-dependently decreased intraocular pressure, multipledoses more than a single dose. Maximal mean ± SEM hypotension after1 dose was 2.5 ± 0.3 mm Hg (0.005% LAT-B; n = 8; P<.001) or 2.7 ± 0.6 mm Hg (0.01% LAT-B; n = 8; P<.005); maximal mean ± SEM hypotension after 9 doses was3.2 ± 0.5 mm Hg (0.005% LAT-B; n = 8; P<.001)or 4.4 ± 0.6 mm Hg (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 notchanged after 1 or 9 doses of 0.01% LAT-B. Miotic and accommodative responsesto intramuscular pilocarpine were dose-dependently inhibited. With 0.02% LAT-B,inhibition of miosis was substantial, whereas the inhibition of accommodationwas only about 25%. With 0.005% LAT-B, the effects were trivial.
In ocular normotensive monkeys, 0.005% and 0.01% LAT-B administeredtopically increases outflow facility and/or decreases intraocular pressurewithout corneal effects. Multiple doses reduce intraocular pressure more thana single dose. Latrunculin-B dose-dependently relaxes the iris sphincter andciliary muscle, with some separation of miotic and accommodative effects.
Multiple treatments with low topical doses of LAT-B may substantiallyreduce outflow resistance in eyes with glaucoma without adversely affectingthe cornea.