Universität zu Köln

Foster, James W., Parikh, Rupin N., Wang, Jiangxia, Bower, Kraig S., Matthaei, Mario, Chakravarti, Shukti, Jun, Albert S., Eberhart, Charles G. and Soiberman, Uri S. (2021). Transcriptomic and Immunohistochemical Analysis of Progressive Keratoconus Reveal Altered WNT10A in Epithelium and Bowman's Layer. Invest. Ophthalmol. Vis. Sci., 62 (6). ROCKVILLE: ASSOC RESEARCH VISION OPHTHALMOLOGY INC. ISSN 1552-5783

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Abstract

PURPOSE. To identify global gene expression changes in the corneal epithelium of keratoconus (KC) patients compared to non-KC myopic controls. METHODS. RNA-sequencing was performed on corneal epithelium samples of five progressive KC and five myopic control patients. Selected results were validated using TaqMan quantitative PCR (qPCR) on 31 additional independent samples, and protein level validation was conducted using western blot analysis on a subset. Immunohistochemistry was performed on tissue microarrays containing cores from over 100 KC and control cases. WNT10A transcript levels in corneal epithelium were correlated with tomographic indicators of KC disease severity in 15 eyes. Additionally, W1V710A was overexpressed in vitro in immortalized corneal epithelial cells. 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 rho = 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Foster, James W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Parikh, Rupin N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Jiangxia UNSPECIFIED UNSPECIFIED UNSPECIFIED Bower, Kraig S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Matthaei, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Chakravarti, Shukti UNSPECIFIED UNSPECIFIED UNSPECIFIED Jun, Albert S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eberhart, Charles G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Soiberman, Uri S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-586955
DOI:	10.1167/iovs.62.6.16
Journal or Publication Title:	Invest. Ophthalmol. Vis. Sci.
Volume:	62
Number:	6
Date:	2021
Publisher:	ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Place of Publication:	ROCKVILLE
ISSN:	1552-5783
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENOME-WIDE ASSOCIATION; CORNEAL EPITHELIUM; DIFFERENTIAL EXPRESSION; PROTEIN-1 SFRP1; COLLAGEN TYPES; TGF-BETA; CATENIN; PROLIFERATION; CURVATURE; PATHWAYS Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58695