Effect of low-dose latrunculin B on anterior segment physiologic features in the monkey eye.

Abstract

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 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.

• Authors: Mehmet Okka, Baohe Tian, Paul L Kaufman
• Journal: Archives of ophthalmology (Chicago, Ill. : 1960) (Arch Ophthalmol) Vol. 122 Issue 10 Pg. 1482-8 (Oct 2004) ISSN: 0003-9950 [Print] United States
• PMID: 15477460 (Publication Type: Duplicate Publication, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• Sympatholytics
• Thiazoles
• Thiazolidines
• Pilocarpine
• latrunculin B

Topics

• Accommodation, Ocular (drug effects)
• Administration, Topical
• Animals
• Anterior Chamber (drug effects, physiology)
• Aqueous Humor (drug effects, physiology)
• Blood Pressure
• Bridged Bicyclo Compounds, Heterocyclic (pharmacology)
• Cornea (cytology, drug effects)
• Female
• Glaucoma (drug therapy)
• Intraocular Pressure (drug effects)
• Macaca fascicularis
• Male
• Pilocarpine (pharmacology)
• Pupil (drug effects, physiology)
• Sympatholytics (pharmacology)
• Thiazoles (pharmacology)
• Thiazolidines