Identifying the role of matrix metalloproteinases in the pathomechanism of TGFBI Arg124Cys related Lattice Corneal Dystrophy Type I

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