In vivo measurement of trabecular meshwork stiffness in a corticosteroid-induced ocular hypertensive mouse model

• Type of Material: Article
• Authors: Guorong Li, Duke University; Chanyoung Lee, Emory University; Vibhuti Agrahari, Shenandoah University; Ke Wang, Emory University; Iris Navarro, Duke University; Joseph M. Sherwood, Imperial College London; Karen Crews, Aerie Pharmaceuticals, Inc.; Sina Farsiu, Duke University; Pedro Gonzalez, Duke University; Cheng-Wen Lin, Aerie Pharmaceuticals, Inc.; Ashim K. Mitra, University of Missouri; Ross Ethier, Emory University; W. Daniel Stamer, Duke University
• Language: English
• Date: 2019-01-29
• Publisher: National Academy of Sciences
• Publication Version: Final Published Version
• Copyright Statement: © 2019 National Academy of Sciences. All Rights Reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1814889116
• Title of Journal or Parent Work: Proceedings of the National Academy of Sciences
• ISSN: 0027-8424
• Volume: 116
• Issue: 5
• Start Page: 1714
• End Page: 1722
• Grant/Funding Information: We acknowledge funding support from the BrightFocus Foundation, Research to Prevent Blindness Foundation, the National Eye Institute (Grants EY005722 and EY019696), and the Georgia Research Alliance.
• Keywords: DEXAMETHASONE; THERAPY; nanoparticle; finite element modeling; GLAUCOMA; OCT; AQUEOUS-HUMOR DYNAMICS; Schlemm's canal; Science & Technology; OUTFLOW FACILITY; Science & Technology - Other Topics; DIABETIC MACULAR EDEMA; Multidisciplinary Sciences; ELASTOGRAPHY; glaucoma; INTRAOCULAR-PRESSURE; MICE; optical coherence tomography
• Research Categories: Engineering, Biomedical; Chemistry, Pharmaceutical; Health Sciences, Opthamology

Abstract

Ocular corticosteroids are commonly used clinically. Unfortunately, their administration frequently leads to ocular hypertension, i.e., elevated intraocular pressure (IOP), which, in turn, can progress to a form of glaucoma known as steroid-induced glaucoma. The pathophysiology of this condition is poorly understood yet shares similarities with the most common form of glaucoma. Using nanotechnology, we created a mouse model of corticosteroid-induced ocular hypertension. This model functionally and morphologically resembles human ocular hypertension, having titratable, robust, and sustained IOPs caused by increased resistance to aqueous humor outflow. Using this model, we then interrogated the biomechanical properties of the trabecular meshwork (TM), including the inner wall of Schlemm’s canal (SC), tissues known to strongly influence IOP and to be altered in other forms of glaucoma. Specifically, using spectral domain optical coherence tomography, we observed that SC in corticosteroid-treated mice was more resistant to collapse at elevated IOPs, reflecting increased TM stiffness determined by inverse finite element modeling. Our noninvasive approach to monitoring TM stiffness in vivo is applicable to other forms of glaucoma and has significant potential to monitor TM function and thus positively affect the clinical care of glaucoma, the leading cause of irreversible blindness worldwide.