Latrunculin-A causes mydriasis and cycloplegia in the cynomolgus monkey

PURPOSE. To determine the effect of latrunculin (LAT)-A, which binds to G-a ctin and disassembles actin filaments, on the pupil, accommodation, and iso lated ciliary muscle (CM) contraction in monkeys. METHODS. Pupil diameter (vernier calipers) and refraction (coincidence refr actometry) were measured every 15 minutes from 0.75 to 3.5 hours after topi cal LAT-A 42 mu g (similar to 10 mu M in the anterior chamber [ACI). Refrac tion was measured every 5 minutes from 0.5 to 1.5 hours after intracameral injection of 10 mu l of 50 mu M LAT-A (similar to 5 mu M in AC), with intra muscular infusion of 1.5 mg/kg pilocarpine HCl (PILO) during the first 15 m inutes of measurements. Pupil diameter was measured at 1 and 2 hours, and r efraction was measured every 5 minutes from 1 to 2 hours, after intravitrea l injection of 20 mu l of 1.25 mM LAT-A (similar to 10 mu M in vitreous), w ith intramuscular infusion of 1.5 mg/kg PILO during the first 15 minutes of measurements (all after topical 2.5% phenylephrine), and contractile respo nse of isolated CM strips, obtained <1 hour postmortem and mounted in a per fusion apparatus, to 10 mu M PILO +/- LAT-A was measured at various concent rations. RESULTS. Topical LAT-A of 42 mu g dilated the pupil without affecting refra ction. Intracameral LAT-A of 5 mu M inhibited miotic and accommodative resp onses to intramuscular PILO. Intravitreal LAT-A of 10 mu M had no effect on accommodative or miotic responses to intramuscular PILO. LAT-A dose-depend ently relaxed the PILO-contracted CM by up to 50% at 3 mu M in both the lon gitudinal and circular vectors. CONCLUSIONS. In monkeys, LAT-A causes mydriasis and cycloplegia, perhaps re lated to its known ability to disrupt the actin microfilament network and c onsequently to affect cell contractility and adhesion. Effects of LAT-A on the iris and CM may have significant physiological and clinical implication s.