Effect of low-dose latrunculin B on anterior segment physiologic features in the monkey eye.
OBJECTIVE
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 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 was 3.2 +/- 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 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.
Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison Medical School, 53792-3284, USA.
Mehmet
M
Okka
Baohe
B
Tian
Paul L
PL
Kaufman
D000065:Accommodation, Ocular / Q000187:drug effects; D000287:Administration, Topical; D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects* / Q000502:physiology*; D001082:Aqueous Humor / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D003315:Cornea / Q000166:cytology / Q000187:drug effects; D005260:Female; D005901:Glaucoma / Q000188:drug therapy; D007429:Intraocular Pressure / Q000187:drug effects*; D008252:Macaca fascicularis; D008297:Male; D010862:Pilocarpine / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects / Q000502:physiology; D013565:Sympatholytics / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
D019086:Bridged Bicyclo Compounds, Heterocyclic; D013565:Sympatholytics; D013844:Thiazoles; D053778:Thiazolidines; D010862:Pilocarpine; C037068:latrunculin B