Latrunculin-A causes mydriasis and cycloplegia in the cynomolgus monkey.

PURPOSE: To determine the effect of latrunculin (LAT)-A, which binds to G-actin and disassembles actin filaments, on the pupil, accommodation, and isolated ciliary muscle (CM) contraction in monkeys.

METHODS

Pupil diameter (vernier calipers) and refraction (coincidence refractometry) were measured every 15 minutes from 0.75 to 3.5 hours after topical LAT-A 42 microg (approximately 10 microM in the anterior chamber [AC]). Refraction was measured every 5 minutes from 0.5 to 1.5 hours after intracameral injection of 10 microl of 50 microM LAT-A (approximately 5 microM in AC), with intramuscular infusion of 1.5 mg/kg pilocarpine HCl (PILO) during the first 15 minutes of measurements. Pupil diameter was measured at 1 and 2 hours, and refraction was measured every 5 minutes from 1 to 2 hours, after intravitreal injection of 20 microl of 1.25 mM LAT-A (approximately 10 microM in vitreous), with intramuscular infusion of 1.5 mg/kg PILO during the first 15 minutes of measurements (all after topical 2.5% phenylephrine), and contractile response of isolated CM strips, obtained <1 hour postmortem and mounted in a perfusion apparatus, to 10 microM PILO +/- LAT-A was measured at various concentrations.

RESULTS

Topical LAT-A of 42 microg dilated the pupil without affecting refraction. Intracameral LAT-A of 5 microM inhibited miotic and accommodative responses to intramuscular PILO. Intravitreal LAT-A of 10 microM had no effect on accommodative or miotic responses to intramuscular PILO. LAT-A dose-dependently relaxed the PILO-contracted CM by up to 50% at 3 microM in both the longitudinal and circular vectors.

CONCLUSIONS

In monkeys, LAT-A causes mydriasis and cycloplegia, perhaps related to its known ability to disrupt the actin microfilament network and consequently to affect cell contractility and adhesion. Effects of LAT-A on the iris and CM may have significant physiological and clinical implications.