2017
DOI: 10.1167/iovs.17-22175
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Estimating Human Trabecular Meshwork Stiffness by Numerical Modeling and Advanced OCT Imaging

Abstract: PurposeThe purpose of this study was to estimate human trabecular meshwork (hTM) stiffness, thought to be elevated in glaucoma, using a novel indirect approach, and to compare results with direct en face atomic force microscopy (AFM) measurements.MethodsPostmortem human eyes were perfused to measure outflow facility and identify high- and low-flow regions (HF, LF) by tracer. Optical coherence tomography (OCT) images were obtained as Schlemm's canal luminal pressure was directly manipulated. TM stiffness was de… Show more

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Cited by 67 publications
(77 citation statements)
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“…These findings are consistent with evidence that Rho-associated protein kinase (ROCK) inhibitors, known to reduce TM actomyosin contractile tone, decrease outflow resistance 14 , 15 . Interestingly, we have also observed a statistically significant inverse correlation between outflow facility and TM stiffness in a previous study using human tissue from both normal and glaucomatous eyes 4 , consistent with the above results. Taken together, these data suggest commonalities between humans and mice in the TM stiffness-outflow resistance relationship.…”
Section: Discussionsupporting
confidence: 92%
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“…These findings are consistent with evidence that Rho-associated protein kinase (ROCK) inhibitors, known to reduce TM actomyosin contractile tone, decrease outflow resistance 14 , 15 . Interestingly, we have also observed a statistically significant inverse correlation between outflow facility and TM stiffness in a previous study using human tissue from both normal and glaucomatous eyes 4 , consistent with the above results. Taken together, these data suggest commonalities between humans and mice in the TM stiffness-outflow resistance relationship.…”
Section: Discussionsupporting
confidence: 92%
“…Specifically, using atomic force microscopy (AFM), TM stiffness was found to be dramatically increased in human glaucomatous eyes compared to that in normal eyes, which was hypothesized to be associated with dysregulation of the extracellular matrix (ECM) observed in glaucoma 1 . Further, in normal and glaucomatous human eyes, we have recently reported an association between outflow facility and TM stiffness as deduced by OCT imaging and numerical modeling 4 . In addition, increased stiffness of TM cells and TM ECM has been reported after exposure to the glucocorticoid dexamethasone (DEX) in cultured human TM cells or in rabbit eyes 5 .…”
Section: Introductionmentioning
confidence: 83%
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“…An unexpected, and potentially important, result of this research was that aqueous drainage pathways continued to functional normally in glaucomatous rat eyes. It is known that trabecular tissue stiffens in human glaucoma [39][40][41] , owing to changes in extracellular matrix properties [42][43][44] and cell mechanobiology 45 . The stiffening is thought to raise IOP by increasing outflow resistance, though experimental support is mixed to date 41,44,46 .…”
Section: Discussionmentioning
confidence: 99%