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Open AccessArticle

Human Keratoconus Cell Contractility is Mediated by Transforming Growth Factor-Beta Isoforms

1
Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
2
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Francesco Puoci
J. Funct. Biomater. 2015, 6(2), 422-438; https://doi.org/10.3390/jfb6020422
Received: 12 May 2015 / Revised: 29 May 2015 / Accepted: 10 June 2015 / Published: 18 June 2015
(This article belongs to the Special Issue Ocular Tissue Engineering)
Keratoconus (KC) is a progressive disease linked to defects in the structural components of the corneal stroma. The extracellular matrix (ECM) is secreted and assembled by corneal keratocytes and regulated by transforming growth factor-β (TGF-β). We have previously identified alterations in the TGF-β pathway in human keratoconus cells (HKCs) compared to normal corneal fibroblasts (HCFs). In our current study, we seeded HKCs and HCFs in 3D-collagen gels to identify variations in contractility, and expression of matrix metalloproteases (MMPs) by HKCs in response the TGF-β isoforms. HKCs showed delayed contractility with decreased Collagen I:Collagen V ratios. TGF-β1 significantly increased ECM contraction, Collagen I, and Collagen V expression by HKCs. We also found that HKCs have significantly decreased Collagen I:Collagen III ratios suggesting a potential link to altered collagen isoform expression in KC. Our findings show that HKCs have significant variations in collagen secretion in a 3D collagen gel and have delayed contraction of the matrix compared to HCFs. For the first time, we utilize a collagen gel model to characterize the contractility and MMP expression by HKCs that may contribute to the pathobiology of KC. View Full-Text
Keywords: keratoconus; transforming growth factor-β; collagen gels; extracellular matrix; matrix metalloproteases keratoconus; transforming growth factor-β; collagen gels; extracellular matrix; matrix metalloproteases
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Lyon, D.; McKay, T.B.; Sarkar-Nag, A.; Priyadarsini, S.; Karamichos, D. Human Keratoconus Cell Contractility is Mediated by Transforming Growth Factor-Beta Isoforms. J. Funct. Biomater. 2015, 6, 422-438.

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