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To whom correspondence may be addressed. Email: ross.ethier@bme.gatech.edu or dan.stamer@duke.edu.

Author contributions: G.L., J.M.S., S.F., P.G., C.-W.L., A.K.M., C.R.E., and W.D.S. designed research; G.L., C.L., V.A., K.W., I.N., K.C., and C.R.E. performed research; V.A., K.C., S.F., C.-W.L., A.K.M., C.R.E., and W.D.S. contributed new reagents/analytic tools; G.L., C.L., K.W., I.N., J.M.S., S.F., P.G., C.-W.L., A.K.M., C.R.E., and W.D.S. analyzed data; and G.L., C.L., K.W., J.M.S., K.C., C.R.E., and W.D.S. wrote the paper.

We thank Ying Hao (Duke Eye Center Core Facility), who prepared histology sections and helped with TEM.

Dr. Vivek Agrahari helped with the preparation and characterization of the NPs.

We also acknowledge Lori Moore (Aerie Pharmaceuticals, Inc.), who helped with delivery of mouse eye samples, and Caroline Wilson, who helped with OCT imaging analysis.

The authors declare no conflict of interest.

Subjects:

Research Funding:

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:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • nanoparticle
  • glaucoma
  • optical coherence tomography
  • finite element modeling
  • Schlemm's canal
  • DIABETIC MACULAR EDEMA
  • AQUEOUS-HUMOR DYNAMICS
  • INTRAOCULAR-PRESSURE
  • OUTFLOW FACILITY
  • DEXAMETHASONE
  • GLAUCOMA
  • MICE
  • ELASTOGRAPHY
  • THERAPY
  • OCT

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

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Journal Title:

Proceedings of the National Academy of Sciences

Volume:

Volume 116, Number 5

Publisher:

, Pages 1714-1722

Type of Work:

Article | Final Publisher PDF

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.

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© 2019 National Academy of Sciences. All Rights Reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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