The relationship between outflow resistance and trabecular meshwork stiffness in mice

• Type of Material: Article
• Authors: Ke Wang, Emory University; Guorong Li, Duke University; A. Thomas Read, Emory University; Iris Navarro, Duke University; Ashim K. Mitra, University of Missouri-Kansas City; W. Daniel Stamer, Duke University; Todd Sulchek, Georgia Institute of Technology; Ross Ethier, Emory University
• Language: English
• Date: 2018-04-11
• Publisher: Nature Publishing Group: Open Access Journals - Option C
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-018-24165-w
• Title of Journal or Parent Work: Scientific Reports
• ISSN: 2045-2322
• Volume: 8
• Start Page: 5848
• End Page: 5848
• Grant/Funding Information: We gratefully acknowledge funding support from the Georgia Research Alliance and the BrightFocus Foundation (GL).
• Keywords: OPEN-ANGLE GLAUCOMA; Multidisciplinary Sciences; MATRIX; Science & Technology; Science & Technology - Other Topics; CELLS; EXPRESSION; INTRAOCULAR-PRESSURE; OCULAR HYPERTENSION; IN-VITRO; DEXAMETHASONE; TISSUE; CILIARY MUSCLE
• Research Categories: Engineering, Biomedical; Health Sciences, Opthamology

Abstract

It has been suggested that common mechanisms may underlie the pathogenesis of primary open-angle glaucoma (POAG) and steroid-induced glaucoma (SIG). The biomechanical properties (stiffness) of the trabecular meshwork (TM) have been shown to differ between POAG patients and unaffected individuals. While features such as ocular hypertension and increased outflow resistance in POAG and SIG have been replicated in mouse models, whether changes of TM stiffness contributes to altered IOP homeostasis remains unknown. We found that outer TM was stiffer than the inner TM and, there was a significant positive correlation between outflow resistance and TM stiffness in mice where conditions are well controlled. This suggests that TM stiffness is intimately involved in establishing outflow resistance, motivating further studies to investigate factors underlying TM biomechanical property regulation. Such factors may play a role in the pathophysiology of ocular hypertension. Additionally, this finding may imply that manipulating TM may be a promising approach to restore normal outflow dynamics in glauco ma. Further, novel technologies are being developed to measure ocular tissue stiffness in situ. Thus, the changes of TM stiffness might be a surrogate marker to help in diagnosing altered conventional outflow pathway function if those technologies could be adapted to TM.