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

Kaitlin C. Murphy, Joshua T. Morgan, Joshua Wood, Adeline Sadeli, Christopher J Murphy, Paul Russell

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)164-171
Number of pages8
JournalExperimental Cell Research
Volume328
Issue number1
DOIs
StatePublished - Oct 15 2014

Fingerprint

Trabecular Meshwork
Actins
rho-Associated Kinases
Glaucoma
Protein Kinase Inhibitors
Cytoskeleton
Actin Cytoskeleton
latrunculin B
Clinical Trials

Keywords

  • Actin
  • Cytoskeleton
  • Latrunculin B
  • Rho-associated protein kinase
  • Trabecular meshwork

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

The formation of cortical actin arrays in human trabecular meshwork cells in response to cytoskeletal disruption. / Murphy, Kaitlin C.; Morgan, Joshua T.; Wood, Joshua; Sadeli, Adeline; Murphy, Christopher J; Russell, Paul.

In: Experimental Cell Research, Vol. 328, No. 1, 15.10.2014, p. 164-171.

Research output: Contribution to journalArticle

Murphy, Kaitlin C. ; Morgan, Joshua T. ; Wood, Joshua ; Sadeli, Adeline ; Murphy, Christopher J ; Russell, Paul. / The formation of cortical actin arrays in human trabecular meshwork cells in response to cytoskeletal disruption. In: Experimental Cell Research. 2014 ; Vol. 328, No. 1. pp. 164-171.
@article{433c45a60b9e4c578f98a54f9b8275db,
title = "The formation of cortical actin arrays in human trabecular meshwork cells in response to cytoskeletal disruption",
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",
author = "Murphy, {Kaitlin C.} and Morgan, {Joshua T.} and Joshua Wood and Adeline Sadeli and Murphy, {Christopher J} and Paul Russell",
year = "2014",
month = "10",
day = "15",
doi = "10.1016/j.yexcr.2014.06.014",
language = "English (US)",
volume = "328",
pages = "164--171",
journal = "Experimental Cell Research",
issn = "0014-4827",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - The formation of cortical actin arrays in human trabecular meshwork cells in response to cytoskeletal disruption

AU - Murphy, Kaitlin C.

AU - Morgan, Joshua T.

AU - Wood, Joshua

AU - Sadeli, Adeline

AU - Murphy, Christopher J

AU - Russell, Paul

PY - 2014/10/15

Y1 - 2014/10/15

N2 - 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.

AB - 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.

KW - Actin

KW - Cytoskeleton

KW - Latrunculin B

KW - Rho-associated protein kinase

KW - Trabecular meshwork

UR - http://www.scopus.com/inward/record.url?scp=84908039943&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908039943&partnerID=8YFLogxK

U2 - 10.1016/j.yexcr.2014.06.014

DO - 10.1016/j.yexcr.2014.06.014

M3 - Article

C2 - 24992043

AN - SCOPUS:84908039943

VL - 328

SP - 164

EP - 171

JO - Experimental Cell Research

JF - Experimental Cell Research

SN - 0014-4827

IS - 1

ER -