Latrunculin-A increases outflow facility in the monkey

PURPOSE. TO determine the effect of Latrunculin (LAT)-A, a macrolide that b inds to G-actin, which leads to the disassembly of actin filaments, on shap e, junctions, and the cytoskeleton of cultured bovine aortic endothelial ce lls (BAECs) and on outflow facility in Living monkeys. METHODS. Latrunculin-A dose-time-response relationships in BAECs were deter mined by immunofluorescence and phase contrast light microscopy, facility b y two-level constant pressure anterior chamber perfusion. RESULTS. In BAECs, LAT-A caused dose- and incubation time-dependent destruc tion of actin bundles, cell separation, and cell loss. Cell- cell adhesions were more sensitive than focal contacts. Recovery was also dose- and time- dependent. In monkeys, exchange intracameral infusion and topical applicati on of LAT-A induced dose- and time-dependent several-fold facility increase s. The facility increase was completely reversed within several hours after drug removal. However, for at least 24 hours after a single topical LAT-A dose, perfusion with drug-free solution caused an accelerated increase in f acility beyond that attributed to normal resistance washout. CONCLUSIONS. Pharmacological disorganization of the actin cytoskeleton in t he trabecular meshwork by specific actin inhibitors like LAT-A may be a use ful antiglaucoma strategy.