Overby, Darryl R. , Zhou, Enhua, Vargas-Pinto, Rocio, Pedrigi, Ryan M. , Fuchshofer, Rudolf , Braakman, Sietse T. , Gupta, Ritika , Perkumas, Kristin M. , Sherwood, Joseph M. , Vahabikashi, Amir , Dang, Quynh , Kim, Jae Hun , Ethier, C. Ross , Stamer, W. Daniel , Fredberg, Jeffrey J. and Johnson, Mark (2014) Schlemm’s canal, pore formation, and outflow dysfunction in glaucoma. PNAS, 111 (38). ISSN 0027-84241091-6490

Abstract

Elevated intraocular pressure, characteristic of glaucoma, is attributable to increased resistance to aqueous humor outflow, but the mechanism of this increased resistance remains unknown. Using endothelial cells isolated from the canal of Schlemm from normal and glaucomatous human eyes, here we establish the existence of a reduced tendency for pore-formation in the glaucomatous cell –likely accounting for increased outflow resistance– together with elevated subcortical cell stiffness, enhanced sensitivity to the mechanical microenvironment, and altered gene expression. Rather than being seen as a simple mechanical barrier, the endothelium of Schlemm’s canal is thus a dynamic material in which pore formation and resulting fluid percolation modulates resistance to aqueous humor outflow. Together, these observations support the idea of cell stiffness –and its biomechanical effects on pore formation– as a therapeutic target in glaucoma.

Item Type:	Article
Date Deposited:	26 Apr 2016 23:45
Last Modified:	26 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/23041