Collagen type XII is undetectable in keratoconus Bowman’s layer

Abstract

PurposeCorneal biomechanical failure is the hallmark of keratoconus (KC); however, the cause of this failure remains elusive. Collagen type XII (COL12A1), which localises to Bowman’s layer (BL), is thought to function in stress-bearing areas, such as BL. Given the putative protective role ofCOL12A1in biomechanical stability, this study aims to characteriseCOL12A1expression in all corneal layers involved in KC.MethodsTaqMan quantitative PCR was performed on 31 corneal epithelium samples of progressive KC and myopic control eyes. Tissue microarrays were constructed using full-thickness corneas from 61 KC cases during keratoplasty and 18 non-KC autopsy eyes and stained with an antibody specific to COL12A1. Additionally,COL12A1was knocked out in vitro in immortalised HEK293 cells.ResultsCOL12A1expression was reduced at transcript levels in KC epithelium compared with controls (ratio: 0.58, p<0.03). Immunohistochemical studies demonstrated that COL12A1 protein expression in BL was undetectable, with reduced expression in KC epithelium, basement membrane and stroma.ConclusionsThe apparent absence of COL12A1 in KC BL, together with the functional importance thatCOL12A1is thought to have in stress bearing areas, suggests thatCOL12A1may play a role in the pathogenesis of KC. Further studies are necessary to investigate the mechanisms that lead toCOL12A1dysregulation in KC.