Altered mechanobiology of Schlemm's canal endothelial cells in glaucoma.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Overby, DR; Zhou, EH; Vargas-Pinto, R; Pedrigi, RM; Fuchshofer, R; Braakman, ST; Gupta, R; Perkumas, KM; Sherwood, JM; Vahabikashi, A; Dang, Q; Kim, JH; Ethier, CR; Stamer, WD; Fredberg, JJ; Johnson, M

Published Date

  • September 23, 2014

Published In

Volume / Issue

  • 111 / 38

Start / End Page

  • 13876 - 13881

PubMed ID

  • 25201985

Pubmed Central ID

  • 25201985

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1410602111

Language

  • eng

Conference Location

  • United States