Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
This PDF is available to Subscribers Only