Latrunculin-A increases outflow facility in the monkey.
OBJECTIVE
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.
Peterson
J A
JA
Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, USA.
Tian
B
B
Bershadsky
A D
AD
Volberg
T
T
Gangnon
R E
RE
Spector
I
I
Geiger
B
B
Kaufman
P L
PL
D000199:Actins / Q000378:metabolism; D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects; D001082:Aqueous Humor / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008387:Marine Toxins / Q000008:administration & dosage / Q000494:pharmacology*; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000494:pharmacology; D011161:Porifera; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D053778:Thiazolidines; D013997:Time Factors; D014129:Trabecular Meshwork / Q000187:drug effects*; D016596:Vinculin / Q000378:metabolism
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015820:Cadherins; D008387:Marine Toxins; D009883:Ophthalmic Solutions; D013844:Thiazoles; D053778:Thiazolidines; D016596:Vinculin; C037067:latrunculin A