Effects of the marine macrolides swinholide A and jasplakinolide on outflow facility in monkeys

PURPOSE. To determine effects of the marine macrolides swin-holide A (Swin A) and jasplakinolide (Jas), alone or in conjunction with latrunculin B (La t B) on outflow facility in monkeys. METHODS. Total outflow facility was measured by two-level constant-pressure perfusion of the anterior chamber before and after exchange with Swin A, J as, or vehicles followed by continuous anterior chamber infusion of drug or vehicle, in opposite eyes of cynomolgus monkeys. The effect of a facility- ineffective dose of Jas plus a threshold or submaximal facility-effective d ose of the actin depolymerizer Lat B on outflow facility was also determine d. RESULTS. Ten or 100 nM Swin A or 20, 100, or 500 nM Jas had no significant effect on outflow facility. However, 500 nM Swin A and 2.5 muM Jas signific antly increased facility by 80% +/- 21 % and 157% +/- 57% (mean +/- SEM) re spectively, adjusted for corresponding baselines and resistance washout in contralateral control eyes. The facility increase in the eye treated with 5 00 nM Jas with 60 or 200 nM Lat B was similar to that in the eye treated wi th 60 or 200 nM Lat B only, CONCLUSIONS. Swin A (which severs actin filaments and sequesters actin dime rs) and Lat B (which sequesters actin monomers) similarly increase outflow facility. The potent inducer of actin polymerization Jas (500 nM) neither i nhibits nor potentiates the facility increase induced by Lat B (60 or 200 n M). A higher dose of Jas increases rather than decreases outflow facility.