Expression of HGF/c‐Met in control and keratoconus corneas

Abstract

AbstractPurpose Keratoconus (KC) is the most common primary degenerative corneal disease with a prevalence of around 1 in 2000 worldwide. A recent genome‐wide association study on potential genes associated with KC identified a significant association between KC and two single nucleotide polymorphisms in the promoter region of the HGF gene. The HGF/c‐Met pathway protects cells from apoptosis and is important to maintain epithelial homeostasis. In this study, we investigated if the HGF/c‐Met pathway is involved in KC by comparing HGF/c‐Met protein expression in control and KC samples.Methods HGF and c‐Met immunoreactivities in control (n=5) and KC (n=10) corneas were imaged by confocal microscopy.Basal tears were collected by capillary micropipettes from control and KC patients (n=5 each), and HGF protein expression determined by Western blot. Intracellular c‐Met (the membrane bound receptor for HGF) expression was detected by extracting proteins from both control and KC corneal epithelium (n=5 each) followed by Western blot.Results HGF and c‐Met were expressed in control and KC corneas. However,in KC obvious cytoplasmic staining of basal epithelium was noted compared to the more diffuse cytoplasmic epithelial immunostaining in control corneas. Western blot results showed that lower levels of HGF in KC tears compared to control tears, and the intracellular c‐Met expression was also weaker in KC cell lysates compared to controls.Conclusion We find that HGF/c‐met expression patterns were altered between KC and control corneas, and their expression levels were reduced in KC tears and corneal epithelium cell lysates suggesting a role for this pathway in the pathogenesis of KC. Funding: Medical School of Sydney University, Sydney Eye Hospital Foundation, Lions NSW Eye Bank