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

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.
Authors	Clayton T McKee, Joshua A Wood, Nihar M Shah, Marion E Fischer, Christopher M Reilly, Christopher J Murphy, Paul Russell
Journal	Biomaterials (Biomaterials) Vol. 32 Issue 9 Pg. 2417-23 (Mar 2011) ISSN: 1878-5905 [Electronic] Netherlands
PMID	21220171 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright	Copyright Â© 2010 Elsevier Ltd. All rights reserved.
Chemical References	Bridged Bicyclo Compounds, Heterocyclic Thiazolidines latrunculin B
Topics	Biomechanical Phenomena (drug effects) Biophysical Phenomena (drug effects) Bridged Bicyclo Compounds, Heterocyclic (pharmacology, therapeutic use) Cell Adhesion (drug effects) Cell Shape (drug effects) Cell Survival (drug effects) Elastic Modulus (drug effects) Glaucoma (drug therapy, pathology) Humans Microscopy, Atomic Force Microscopy, Fluorescence Thiazolidines (pharmacology, therapeutic use) Trabecular Meshwork (drug effects, pathology)

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