Changes in Fibroblast Mechanostat Set Point and Mechanosensitivity: An Adaptive Response to Mechanical Stress in Floppy Eyelid Syndrome

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.