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Changes in fibroblast mechanostat set point and mechanosensitivity: an adaptive response to mechanical stress in floppy eyelid syndrome.

Abstract：

PURPOSE:Floppy eyelid syndrome (FES) is an acquired hyperelasticity disorder affecting the upper eyelid. The tarsal plate becomes hyperelastic with a loss of intrinsic rigidity. As a result, the eyelid is subjected to cyclic mechanical stress. This condition was used as a model to investigate changes in dynamic fibroblast contractility in the context of chronic cyclic mechanical stress. METHODS:Contractile efficiency was investigated in a free-floating, three-dimensional collagen matrix model. Intrinsic cellular force measurements and responses to changes in gel tension were explored using a tensioning culture force monitor (t-CFM). Gene expression differences between cell lines exhibiting differences in contractile phenotype were explored with a genome level microarray platform and RT-PCR. RESULTS:FES tarsal plate fibroblasts (TFs) showed an increased contractile efficiency compared with the control, and t-CFM measurements confirmed a higher intrinsic cellular force at plateau levels. Cyclic stretch/relaxation experiments determined that TFs in FES maintained a functional tensional homeostasis response but with an altered sensitivity, operating around a higher mechanostat set point. Gene expression array and RT-PCR analysis identified V-CAM1 and PPP1R3C as being upregulated in FES TFs. CONCLUSIONS:These changes may represent an adaptive response that allows tensional homeostasis to be maintained at the high levels of tissue stress experienced in FES. Gene expression studies point to a role for V-CAM1 and PPP1R3C in mediating changes in the dynamic range of mechanosensitivity of TFs. This work identifies FES as a useful model for the study of adaptive physiological responses to mechanical stress.

journal_name

Invest Ophthalmol Vis Sci

journal_title

Investigative ophthalmology & visual science

authors

Ezra DG,Ellis JS,Beaconsfield M,Collin R,Bailly M

doi

10.1167/iovs.09-4724

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

3853-63

issue

eissn

0146-0404

issn

1552-5783

pii

iovs.09-4724

journal_volume

pub_type

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Changes in fibroblast mechanostat set point and mechanosensitivity: an adaptive response to mechanical stress in floppy eyelid syndrome.