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Baiyun Liu, Jason Kilpatrick, Bartlomiej Lukasz, Deborah Wallace, Abbot Clark, Colm O'Brien, Suzanne Jarvis; The Influence of Substrate Stiffness on the Proliferation and Mechanical Properties of Normal and Glaucoma Trabecular Meshwork (NTM and GTM) Cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):60. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Previous work (Last et al, 2011) has shown that the mechanical properties of the Human Trabecular Meshwork (HTM) changes dramatically during the progression of glaucoma. Stiffness of the substratum has been demonstrated to influence a wide range of fundamental cell behaviours including cell morphology, mechanical properties and differentiation. The purpose of this study was to determine the influence of substrate stiffness on the proliferation, morphology, and mechanical properties of normal trabecular meshwork (NTM) and glaucoma trabecular meshwork (GTM) cells.
NTM and GTM cells were grown on substrates with a stiffness of 5kPa and 100kPa, which mimic the mechanical properties of the normal and glaucomatous human trabecular meshwork, respectively. Atomic force microscopy (AFM) was used to measure the elastic moduli of NTM and GTM cells on both substrates. Cell shape and morphology were also identified using immunohistochemistry.
The morphology of NTM cells which adhered to the glaucomatous (pathomimetic) substrates (100kPa) were predominantly elongated in appearance, compared with NTM on the normal (homeomimetic) substrates (5kPa), which appeared predominately round. GTM cells, however, did not exhibit significant difference in cell morphology when grown on the homeomimetic or pathomimetic substrates. Additionally, the measured elastic moduli of HTM cells grown on pathomimetic and homeomimetic substrates differed dramatically. Differences in cytoskeletal architecture between cells on pathomimetic and homeomimetic surfaces were also observed.
Cellular response to substrate stiffness suggests that alterations in meshwork mechanical properties associated with glaucoma alter NTM but not GTM cell morphology. Additionally, substratum conditions which mimic the changes in environment associated with glaucoma alter the stiffness of both NTM and GTM cells.
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