Purchase this article with an account.
X Liu, CR Brandt, JR Polansky, PL Kaufman; Latrunculin-A Concentrations Subthreshold for Increasing Outflow Facility in Monkeys Inhibit Dexamethasone-Induced Changes in Cytoskeleton and Focal Adhesions in Cultured HTM Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4090.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the effects of latrunculin (LAT)-A, at a dose subthreshold for increasing outflow facility in monkeys, on dexamethasone (DEX)-induced cross-linked actin networks (CLANs) and changes in focal adhesions in cultured human trabecular meshwork (HTM) cells. Methods: HTM cells were cultured to a highly confluent stage with stable endothelium-like morphology and exposed to 100 nM DEX and/or 0.1 µM LAT-A. Changes in the actin cytoskeleton and vinculin-containing focal contacts were evaluated by immunofluorescence microscopy. Results: DEX induced typical CLANs in normal HTM cells within 5 days which progressed during the 19-day observation period, but failed to induce CLANs for at least 4 wk when co-treated with LAT-A. DEX failed to induce CLANs for at least 2 wk when pre-treated with LAT-A for 2 wk, even if LAT-A was removed before DEX was added. Experiments to determine whether LAT-A can reverse DEX-induced cytoskeletal changes are in progress. HTM cells treated with 0.1 µM LAT-A for 5 days showed mild disorganization of the actin cytoskeleton and focal adhesions, which did not progress for the 4 wk of treatment. Conclusion: Although LAT-A is not a DEX antagonist, it is able to prevent effects of DEX on the actin cytoskeleton in cultured HTM cells at a dose subthreshold for increasing outflow facility in live monkeys and for disrupting the actin cytoskeleton and associated cellular adhesions in cultured HTM cells. These results suggest that LAT-A at low doses may be useful in treating steroid and other glaucomas.
This PDF is available to Subscribers Only