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Regulation of scleral cell contraction by transforming growth factor-β and stress competing roles in myopic growth

Jobling, Andrew I., Gentle, Alex, Metlapally, Ravikanth, McGowan, Bryan J. and McBrien, Neville A. 2008, Regulation of scleral cell contraction by transforming growth factor-β and stress competing roles in myopic growth, Journal of biological chemistry, vol. 284, pp. 2072-2079.

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Title Regulation of scleral cell contraction by transforming growth factor-β and stress competing roles in myopic growth
Author(s) Jobling, Andrew I.
Gentle, AlexORCID iD for Gentle, Alex orcid.org/0000-0003-0661-4196
Metlapally, Ravikanth
McGowan, Bryan J.
McBrien, Neville A.
Journal name Journal of biological chemistry
Volume number 284
Start page 2072
End page 2079
Total pages 8
Publisher PubMed Central
Place of publication Manchester, Eng.
Publication date 2008-01-23
ISSN 1083-351X
Summary Reduced extracellular matrix accumulation in the sclera of myopic eyes leads to increased ocular extensibility and is related to reduced levels of scleral transforming growth factor-β (TGF-β). The current study investigated the impact of this extracellular environment on scleral cell phenotype and cellular biomechanical characteristics. Scleral cell phenotype was investigated in vivo in a mammalian model of myopia using the myofibroblast marker, α-smooth muscle actin (α-SMA). In eyes developing myopia α-SMA levels were increased, suggesting increased numbers of contractile myofibroblasts, and decreased in eyes recovering from myopia. To understand the factors regulating this change in scleral phenotype, the competing roles of TGF-β and mechanical stress were investigated in scleral cells cultured in three-dimensional collagen gels. All three mammalian isoforms of TGF-β altered scleral cell phenotype to produce highly contractile, α-SMA-expressing myofibroblasts (TGF-β3 > TGF-β2 > TGF-β1). Exposure of cells to the reduced levels of TGF-β found in the sclera in myopia produced decreased cell-mediated contraction and reduced α-SMA expression. These findings are contrary to the in vivo gene expression data. However, when cells were exposed to both the increased stress and the reduced levels of TGF-β found in myopia, increased α-SMA expression was observed, replicating in vivo findings. These results show that although reduced scleral TGF-β is a major contributor to the extracellular matrix remodeling in the myopic eye, it is the resulting increase in scleral stress that dominates the competing TGF-β effect, inducing increased α-SMA expression and, hence, producing a larger population of contractile cells in the myopic eye.
Language eng
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2008, PubMed Central
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30064473

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.