December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Latrunculin-A Concentrations Subthreshold for Increasing Outflow Facility in Monkeys Inhibit Dexamethasone-Induced Changes in Cytoskeleton and Focal Adhesions in Cultured HTM Cells
Author Affiliations & Notes
  • X Liu
    Ophthalmology & Visual Sciences University of Wisconsin Madison WI
  • CR Brandt
    Ophthalmology & Visual Sciences University of Wisconsin Madison WI
  • JR Polansky
    Ophthalmology University of California San Francisco CA
  • PL Kaufman
    Ophthalmology & Visual Sciences University of Wisconsin Madison WI
  • Footnotes
    Commercial Relationships   X. Liu, None; C.R. Brandt, None; J.R. Polansky, None; P.L. Kaufman, University of Wisconsin P. Grant Identification: Support: NEI EY02698 and EY02477, AHAF, RPB, GRF
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 4090. doi:
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      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.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : 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.

Keywords: 390 drug toxicity/drug effects • 601 trabecular meshwork • 383 cytoskeleton 
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