Collagen type XII is undetectable in keratoconus Bowman's layer

圆锥角膜鲍曼层中未检测到 XII 型胶原蛋白

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作者:Mohammed Rigi #, Hyeck-Soo Son #, Loren Moon, Mario Matthaei, Divya Srikumaran, Albert S Jun, Charles G Eberhart, Uri S Soiberman

Conclusions

The apparent absence of COL12A1 in KC BL, together with the functional importance that COL12A1 is thought to have in stress bearing areas, suggests that COL12A1 may play a role in the pathogenesis of KC. Further studies are necessary to investigate the mechanisms that lead to COL12A1 dysregulation in KC.

Methods

TaqMan 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, COL12A1 was knocked out in vitro in immortalised HEK293 cells.

Purpose

Corneal 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 of COL12A1 in biomechanical stability, this study aims to characterise COL12A1 expression in all corneal layers involved in KC.

Results

COL12A1 expression 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. Conclusions: The apparent absence of COL12A1 in KC BL, together with the functional importance that COL12A1 is thought to have in stress bearing areas, suggests that COL12A1 may play a role in the pathogenesis of KC. Further studies are necessary to investigate the mechanisms that lead to COL12A1 dysregulation in KC.

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