The effect of biophysical attributes of the ocular trabecular meshwork associated with glaucoma on the cell response to therapeutic agents

Clayton T. McKee, Joshua Wood, Nihar M. Shah, Marion E. Fischer, Christopher M. Reilly, Christopher J Murphy, Paul Russell

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Glaucoma is a devastating neurodegenerative disease, which can lead to vision loss and is associated with irreversible damage to retinal ganglion cells. Although the mechanism of disease onset remains unknown, we have recently demonstrated that the stiffness of the ocular trabecular meshwork (HTM) increases dramatically in human donor eyes with a history of glaucoma. Here we report that polyacrylamide hydrogels, which mimic the compliant conditions of normal and glaucomatous HTM, profoundly modulate cytoskeletal dynamics and the elastic modulus of the overlying HTM cells. Substratum compliance also modulates HTM cell response to Latrunculin-B, a cytoskeletal disrupting agent currently in human clinical trials for the treatment of glaucoma. Additionally, we observed a compliance-dependent rebound effect of Latrunculin-B with an unexpected increase in HTM cell elastic modulus being observed upon withdrawal of the drug. The results predict that cytoskeletal disrupting drugs may be more potent in advanced stages of glaucoma.

Original languageEnglish (US)
Pages (from-to)2417-2423
Number of pages7
JournalBiomaterials
Volume32
Issue number9
DOIs
StatePublished - Mar 2011

Keywords

  • AFM
  • Biophysical attributes
  • Extracellular matrix
  • Glaucoma
  • Latrunculin
  • Young's modulus

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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