Transcriptomic and Immunohistochemical Analysis of Progressive Keratoconus Reveal Altered WNT10A in Epithelium and Bowman's Layer

进行性圆锥角膜的转录组学和免疫组织化学分析显示上皮和鲍曼层中的 WNT10A 发生改变

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作者:James W Foster, Rupin N Parikh, Jiangxia Wang, Kraig S Bower, Mario Matthaei, Shukti Chakravarti, Albert S Jun, Charles G Eberhart, Uri S Soiberman

Conclusions

A specific Wnt ligand, WNT10A, is reduced at the mRNA and protein level in KC epithelium and Bowman's layer. This ligand positively regulates collagen type I expression in corneal epithelial cells. The results suggest that WNT10A expression in the corneal epithelium may play a role in progressive KC.

Methods

RNA-sequencing was performed on corneal epithelium samples of five progressive KC and five myopic control patients. Selected

Purpose

To identify global gene expression changes in the corneal epithelium of keratoconus (KC) patients compared to non-KC myopic controls.

Results

WNT10A was found to be underexpressed in KC epithelium at the transcript (ratio KC/control = 0.59, P = 0.02 per RNA-sequencing study; ratio = 0.66, P = 0.03 per qPCR) and protein (ratio = 0.07, P = 0.06) levels. Immunohistochemical analysis also indicated WNT10A protein was decreased in Bowman's layer of KC patients. In contrast, WNT10A transcript level positively correlated with increased keratometry (Kmax ρ = 0.57, P = 0.02). Finally, WNT10A positively regulated COL1A1 expression in corneal epithelial cells. Conclusions: A specific Wnt ligand, WNT10A, is reduced at the mRNA and protein level in KC epithelium and Bowman's layer. This ligand positively regulates collagen type I expression in corneal epithelial cells. The results suggest that WNT10A expression in the corneal epithelium may play a role in progressive KC.

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