Latrunculin-A increases outflow facility in the monkey.

Abstract:

PURPOSE:To determine the effect of Latrunculin (LAT)-A, a macrolide that binds to G-actin, which leads to the disassembly of actin filaments, on shape, junctions, and the cytoskeleton of cultured bovine aortic endothelial cells (BAECs) and on outflow facility in living monkeys. METHODS:Latrunculin-A dose-time-response relationships in BAECs were determined by immunofluorescence and phase contrast light microscopy, facility by two-level constant pressure anterior chamber perfusion. RESULTS:In BAECs, LAT-A caused dose- and incubation time- dependent destruction 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 application of LAT-A induced dose- and time-dependent several-fold facility increases. 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 facility beyond that attributed to normal resistance washout. CONCLUSIONS:Pharmacological disorganization of the actin cytoskeleton in the trabecular meshwork by specific actin inhibitors like LAT-A may be a useful antiglaucoma strategy.

authors

Peterson JA,Tian B,Bershadsky AD,Volberg T,Gangnon RE,Spector I,Geiger B,Kaufman PL

keywords:

subject

Has Abstract

pub_date

1999-04-01 00:00:00

pages

931-41

issue

5

eissn

0146-0404

issn

1552-5783

journal_volume

40

pub_type

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