The formation of cortical actin arrays in human trabecular meshwork cells in response to cytoskeletal disruption

Exp Cell Res. 2014 Oct 15;328(1):164-171. doi: 10.1016/j.yexcr.2014.06.014. Epub 2014 Jun 30.

Abstract

The cytoskeleton of human trabecular meshwork (HTM) cells is known to be altered in glaucoma and has been hypothesized to reduce outflow facility through contracting the HTM tissue. Latrunculin B (Lat-B) and Rho-associated protein kinase (ROCK) inhibitors disrupt the actin cytoskeleton and are in clinical trials as glaucoma therapeutics. We have previously reported a transient increase in HTM cell stiffness peaking at 90 min after Lat-B treatment with a return to pretreatment values after 270 min. We hypothesize that changes in actin morphology correlate with alterations in cell stiffness induced by Lat-B but this is not a general consequence of other cytoskeletal disrupting agents such as Rho kinase inhibitors. We treated HTM cells with 2 µM Lat-B or 100 µM Y-27632 and allowed the cells to recover for 30-270 min. While examining actin morphology in Lat-B treated cells, we observed striking cortical actin arrays (CAAs). The percentage of CAA positive cells (CPCs) was time dependent and exceeded 30% at 90 min and decreased after 270 min. Y-27632 treated cells exhibited few CAAs and no changes in cell stiffness. Together, these data suggest that the increase in cell stiffness after Lat-B treatment is correlated with CAAs.

Keywords: Actin; Cytoskeleton; Latrunculin B; Rho-associated protein kinase; Trabecular Meshwork.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Amides / pharmacology
  • Antihypertensive Agents / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Cell Physiological Phenomena
  • Cells, Cultured
  • Cytoskeleton / drug effects*
  • Cytoskeleton / metabolism
  • Humans
  • Image Processing, Computer-Assisted
  • Pyridines / pharmacology
  • Thiazolidines / pharmacology*
  • Trabecular Meshwork / cytology*
  • Trabecular Meshwork / drug effects
  • rho-Associated Kinases / antagonists & inhibitors

Substances

  • Actins
  • Amides
  • Antihypertensive Agents
  • Bridged Bicyclo Compounds, Heterocyclic
  • Pyridines
  • Thiazolidines
  • Y 27632
  • rho-Associated Kinases
  • latrunculin B