The Effect of Biophysical Attributes of the Ocular Trabecular Meshwork Associated with Glaucoma on the Cell Response to Therapeutic Agents

Overview

Journal Biomaterials

Specialty Biomedical Engineering

Date 2011 Jan 12

PMID 21220171

Citations 53

Authors

Clayton T McKee

Joshua A Wood

Nihar M Shah

Marion E Fischer

Christopher M Reilly

Christopher J Murphy

Paul Russell

Affiliations

Soon will be listed here.

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.

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