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

Guorong Li, Chanyoung Lee, Vibhuti Agrahari, Ke Wang, Iris Navarro, Joseph M. Sherwood, Karen Crews, Sina Farsiu, Pedro Gonzalez, Cheng Wen Lin, Ashim K. Mitra, C. Ross Ethier, W. Daniel Stamer

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1714-1722
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number5
DOIs
StatePublished - Jan 29 2019
Externally publishedYes

Keywords

  • Finite element modeling
  • Glaucoma
  • Nanoparticle
  • Optical coherence tomography
  • Schlemm’s canal

ASJC Scopus subject areas

  • General

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