Effects of latrunculin B on outflow facility, intraocular pressure, corneal thickness, and miotic and accommodative responses to pilocarpine in monkeys.
OBJECTIVE
To determine if low doses of topical latrunculin B (LAT-B) will increase outflow facility and decrease intraocular pressure (IOP) without adversely affecting the cornea, and inhibit miotic and accommodative responses to pilocarpine, in ocular normotensive monkeys.


METHODS
Intraocular pressure was measured by Goldmann tonometry before and after one and nine dose(s) of 0.005% and 0.01% topical LAT-B/vehicle given twice daily on successive weeks. Outflow facility was then measured by perfusion following 15 doses. Central corneal thickness was measured by ultrasonic pachymetry before and after one and nine dose(s) of 0.01% LAT-B/vehicle. Pupillary diameter (calipers) and accommodation (refractometry) before and after one dose of 0.005% and 0.02% LAT-B were determined.


RESULTS
LAT-B dose-dependently decreased IOP, multiple doses more than a single dose. Maximal hypotension after one 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 hypotension after nine 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 75 +/- 13% (n = 7; P < .005). Central corneal thickness was not changed after one or nine dose(s) of 0.01% LAT-B. The miotic and accommodative responses to intramuscular pilocarpine were dose-dependently inhibited. At 0.02% LAT-B, the inhibition of miosis was essentially complete when compared with the pre-LAT-B value, whereas the inhibition of accommodation was only about 25%. At 0.005% LAT-B, the effects were trivial.


CONCLUSIONS
In ocular normotensive monkeys, 0.005/0.01% LAT-B administered topically increases outflow facility and/or decreases IOP, but does not affect the cornea. Multiple doses reduce IOP more than a single dose. LAT-B dose-dependently relaxes the iris sphincter and ciliary muscle, with some separation of the miotic and accommodative effects.
Okka
Mehmet
M
Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, Wisconsin, USA.
Tian
Baohe
B
Kaufman
Paul L
PL
D000065:Accommodation, Ocular / Q000187:drug effects*; D000287:Administration, Topical; D000818:Animals; D000869:Anterior Eye Segment / Q000502:physiology*; D001082:Aqueous Humor / Q000502:physiology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000494:pharmacology*; D003315:Cornea / Q000033:anatomy & histology* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D008540:Meiosis / Q000187:drug effects*; D008916:Miotics / Q000494:pharmacology*; D010862:Pilocarpine / Q000494:pharmacology*; D011680:Pupil / Q000187:drug effects; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D053778:Thiazolidines
D019086:Bridged Bicyclo Compounds, Heterocyclic; D008916:Miotics; D013844:Thiazoles; D053778:Thiazolidines; D010862:Pilocarpine; C037068:latrunculin B