April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Identifying the role of matrix metalloproteinases in the pathomechanism of TGFBI Arg124Cys related Lattice Corneal Dystrophy Type I
Author Affiliations & Notes
  • Johnny E Moore
    School of Biomedical Scences, University of Ulster, Coleraine, United Kingdom
  • David G Courtney
    School of Biomedical Scences, University of Ulster, Coleraine, United Kingdom
  • Sarah D Atkinson
    School of Biomedical Scences, University of Ulster, Coleraine, United Kingdom
    Dermatology and Genetic Medicine, University of Dundee, Dundee, United Kingdom
  • Eleonora Maurizi
    School of Biomedical Scences, University of Ulster, Coleraine, United Kingdom
    Centre for Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
  • Andrew M Nesbit
    School of Biomedical Scences, University of Ulster, Coleraine, United Kingdom
  • Graziella Pellegrini
    Centre for Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy
  • Dimitri T Azar
    Department of Ophthalmology and Visual Sciences, University of Illinois College of Medicine at Chicago, Chicago, IL
  • Irwin W McLean
    Dermatology and Genetic Medicine, University of Dundee, Dundee, United Kingdom
  • Tara C B Moore
    School of Biomedical Scences, University of Ulster, Coleraine, United Kingdom
    Dermatology and Genetic Medicine, University of Dundee, Dundee, United Kingdom
  • Footnotes
    Commercial Relationships Johnny Moore, None; David Courtney, None; Sarah Atkinson, None; Eleonora Maurizi, None; Andrew Nesbit, None; Graziella Pellegrini, None; Dimitri Azar, None; Irwin McLean, None; Tara Moore, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1011. doi:
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      Johnny E Moore, David G Courtney, Sarah D Atkinson, Eleonora Maurizi, Andrew M Nesbit, Graziella Pellegrini, Dimitri T Azar, Irwin W McLean, Tara C B Moore; Identifying the role of matrix metalloproteinases in the pathomechanism of TGFBI Arg124Cys related Lattice Corneal Dystrophy Type I. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1011.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: This study was designed to investigate whether matrix metalloproteinases (MMPs) play a pivotal role in the development of TGFBI-Arg124Cys lattice corneal dystrophy type I (LCDI) using an ex vivo model of LCDI corneal epithelial cell cultures and corneal tissue excised from an LCDI patient.

Methods: To initially determine whether the dissolution of Bowman’s layer is apparent in an LCDI affected cornea an H&E stain was carried out on sections of a corneal button excised from a patient suffering from TGFBI-Arg124Cys LCDI. Immunohistochecimstry (IHC) was also carried out to determine whether there is a localisation of MMPs around Bowman’s layer. To confirm the induction of MMPs due to the presence of the TGFBI-Arg124Cys mutant allele qRT-PCR was carried out on LCDI corneal epithelial cultures and expression levels were compared to those observed in wild type corneal epithelial cultures.

Results: H&E staining confirmed dissolution of Bowman’s layer in an LCDI affected cornea while IHC staining revealed a localisation of MMPs around Bowman’s layer. MMP expression levels were also found to be significantly increased at the mRNA level in the LCDI corneal epithelial cultures.

Conclusions: The induction of MMP expression observed in the LCDI corneal epithelial cultures coupled with the H&E and IHC MMP staining indicates that MMPs may play a pivotal role in the development of TGFBI-Arg124Cys LCDI. Further investigation into silencing the TGFBI-Arg124Cys allele in LCDI corneal epithelial cultures and determining whether this has an inhibitory effect on MMP expression would further substantiate the concept that MMPs play a pivotal role in the onset of TGFBI-Arg124Cys LCDI.

Keywords: 482 cornea: epithelium • 519 extracellular matrix • 533 gene/expression  
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