Altered mechanobiology of Schlemm's canal endothelial cells in glaucoma

Darryl R. Overby, Enhua H. Zhou, Rocio Vargas-Pinto, Ryan M. Pedrigi, Rudolf Fuchshofer, Sietse T. Braakman, Ritika Gupta, Kristin M. Perkumas, Joseph M. Sherwood, Amir Vahabikashi, Quynh Dang, Jae Hun Kim, C. Ross Ethier, W. Daniel Stamer, Jeffrey J. Fredberg, Mark Johnson*

*Corresponding author for this work

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Increased flow resistance is responsible for the elevated intraocular pressure characteristic of glaucoma, but the cause of this resistance increase is not known. We tested the hypothesis that altered biomechanical behavior of Schlemm's canal (SC) cells contributes to this dysfunction. We used atomic force microscopy, optical magnetic twisting cytometry, and a unique cell perfusion apparatus to examine cultured endothelial cells isolated from the inner wall of SC of healthy and glaucomatous human eyes. Here we establish the existence of a reduced tendency for pore formation in the glaucomatous SC cell-likely accounting for increased outflow resistance-that positively correlates with elevated subcortical cell stiffness, along with an enhanced sensitivity to the mechanical microenvironment including altered expression of several key genes, particularly connective tissue growth factor. Rather than being seen as a simple mechanical barrier to filtration, the endothelium of SC is seen instead as a dynamic material whose response to mechanical strain leads to pore formation and thereby modulates the resistance to aqueous humor outflow. In the glaucomatous eye, this process becomes impaired. Together, these observations support the idea of SC cell stiffness-and its biomechanical effects on pore formation-as a therapeutic target in glaucoma.

Original languageEnglish (US)
Pages (from-to)13876-13881
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number38
DOIs
StatePublished - Sep 23 2014

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Altered mechanobiology of Schlemm's canal endothelial cells in glaucoma'. Together they form a unique fingerprint.

  • Cite this

    Overby, D. R., Zhou, E. H., Vargas-Pinto, R., Pedrigi, R. M., Fuchshofer, R., Braakman, S. T., Gupta, R., Perkumas, K. M., Sherwood, J. M., Vahabikashi, A., Dang, Q., Kim, J. H., Ethier, C. R., Daniel Stamer, W., Fredberg, J. J., & Johnson, M. (2014). Altered mechanobiology of Schlemm's canal endothelial cells in glaucoma. Proceedings of the National Academy of Sciences of the United States of America, 111(38), 13876-13881. https://doi.org/10.1073/pnas.1410602111