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Differential epithelial and stromal protein profiles in cone and non-cone regions of keratoconus corneas.

Abstract：

:Keratoconus (KC) is an ectatic corneal disease characterized by progressive thinning and irregular astigmatism, and a leading indication for corneal transplantation. KC-associated changes have been demonstrated for the entire cornea, but the pathological thinning and mechanical weakening is usually localized. We performed quantitative proteomics using Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectrometry (SWATH-MS) to analyze epithelial and stromal changes between the topographically-abnormal cone and topographically-normal non-cone regions of advanced KC corneas, compared to age-matched normal corneas. Expression of 20 epithelial and 14 stromal proteins was significantly altered (≥2 or ≤0.5-fold) between cone and non-cone in all 4 KC samples. Ingenuity pathway analysis illustrated developmental and metabolic disorders for the altered epithelial proteome with mitochondrion as the significant gene ontology (GO) term. The differential stromal proteome was related to cellular assembly, tissue organization and connective tissue disorders with endoplasmic reticulum protein folding as the significant GO term. Validation of selected protein expression was performed on archived KC, non-KC and normal corneal specimens by immunohistochemistry. This is the first time to show that KC-associated proteome changes were not limited to the topographically-thinner and mechanically-weakened cone but also non-cone region with normal topography, indicating a peripheral involvement in KC development.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Yam GH,Fuest M,Zhou L,Liu YC,Deng L,Chan AS,Ong HS,Khor WB,Ang M,Mehta JS

doi

10.1038/s41598-019-39182-6

subject

Has Abstract

pub_date

2019-02-27 00:00:00

pages

2965

issue

1

issn

2045-2322

pii

10.1038/s41598-019-39182-6

journal_volume

9

pub_type

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