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

• Published in: Investigative ophthalmology & visual science 2010-08, Vol.51 (8), p.3853-3863
• Main Authors: Ezra, Daniel G, Ellis, James S, Beaconsfield, Michèle, Collin, Richard, Bailly, Maryse
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Adaptation, Physiological; Carrier Proteins - genetics; Eyelid Diseases - genetics; Eyelid Diseases - metabolism; Eyelid Diseases - physiopathology; Fibroblasts - physiology; Fluorescent Antibody Technique, Indirect; Gene Expression Regulation - physiology; Humans; Intracellular Signaling Peptides and Proteins; Mechanotransduction, Cellular - physiology; Microscopy, Confocal; Muscle Contraction - physiology; Muscle Hypotonia - genetics; Muscle Hypotonia - metabolism; Muscle Hypotonia - physiopathology; Oligonucleotide Array Sequence Analysis; Phosphoprotein Phosphatases - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Stress, Mechanical; Syndrome; Vascular Cell Adhesion Molecule-1 - genetics
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.09-4724

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. 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. 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. 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.