Research Papers:

The intrinsic stiffness of human trabecular meshwork cells increases with senescence

Joshua T. Morgan, Vijay Krishna Raghunathan, Yow-Ren Chang, Christopher J. Murphy and Paul Russell _

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Oncotarget. 2015; 6:15362-15374. https://doi.org/10.18632/oncotarget.3798

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Joshua T. Morgan1,*, Vijay Krishna Raghunathan1,*, Yow-Ren Chang1, Christopher J. Murphy1,2 and Paul Russell1

1 Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA

2 Department of Ophthalmology & Vision Science, School of Medicine, University of California, Davis, CA, USA

* These authors have contributed equally to this work

Correspondence to:

Paul Russell, email:

Keywords: trabecular meshwork, senescence, mechanobiology, cytoskeleton

Received: February 28, 2015 Accepted: March 20, 2015 Published: April 12, 2015


Dysfunction of the human trabecular meshwork (HTM) plays a central role in the age-associated disease glaucoma, a leading cause of irreversible blindness. The etiology remains poorly understood but cellular senescence, increased stiffness of the tissue, and the expression of Wnt antagonists such as secreted frizzled related protein-1 (SFRP1) have been implicated. However, it is not known if senescence is causally linked to either stiffness or SFRP1 expression. In this study, we utilized in vitro HTM senescence to determine the effect on cellular stiffening and SFRP1 expression. Stiffness of cultured cells was measured using atomic force microscopy and the morphology of the cytoskeleton was determined using immunofluorescent analysis. SFRP1 expression was measured using qPCR and immunofluorescent analysis. Senescent cell stiffness increased 1.88±0.14 or 2.57±0.14 fold in the presence or absence of serum, respectively. This was accompanied by increased vimentin expression, stress fiber formation, and SFRP1 expression. In aggregate, these data demonstrate that senescence may be a causal factor in HTM stiffening and elevated SFRP1 expression, and contribute towards disease progression. These findings provide insight into the etiology of glaucoma and, more broadly, suggest a causal link between senescence and altered tissue biomechanics in aging-associated diseases.

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