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Gary Hin-Fai Yam, Matthias Fuest, Lei Zhou, Marcus Ang, Jodhbir S Mehta; Keratoconus proteome: epithelial and stromal changes in cone and non-cone regions. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4381.
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© ARVO (1962-2015); The Authors (2016-present)
Keratoconus (KC), an asymmetric ectatic corneal disorder with progressive central thinning and protrusion, leading to astigmatism, scarring and vision loss. It has been considered as degeneration but recent proteomics studies have associated KC as an immunological disorder. Here, we studied the proteomic changes within KC epithelium and stroma, by separating the central cornea into cone-containing and non-cone regions.
Five KC central corneas were carefully dissected to cone and non-cone regions with reference to pre-operative topographic assessment. Epithelial and stromal proteins were harvested for label-free SWATH mass spectrometry. Data were processed using ProteinPilot v5.0 and compared among cone, non-cone regions and normal corneas with cut-off at ≥2 and ≤0.5-fold. Enriched gene ontology, biological pathways and disease association were examined by DAVID, IMPaLA and Ingenuity Pathway Analysis.
We studied epithelial and stromal proteomes of (1) KC (cone and non-cone) versus normal, (2) non-cone versus normal, and (3) cone versus non-cone samples. KC epithelial proteomes affected canonical pathways including cell adhesion, cellular assembly, mitochondrial functions, mRNA/rRNA processing and decay, translation, developmental and metabolic disorders. KC stromal proteomes regulated complement activation and cascades, endopeptidase activity, protein folding, dermatological, inflammatory and immunological disorders. We analysed top 50 significantly increased and decreased proteins in cone versus non-cone versus normal samples. The significant biotomes related to non-cone epithelial changes were ATP synthesis, respiratory electron transport and neutrophil degranulation. Additional immune system, metabolism and senescence pathways were linked to cone stage. Non-cone stromal changes were related to complement cascade, B-cell receptor regulation, Fcγ receptor activation and immune system. Additional pathways (FCERI-mediated NFκb activation and Ca++ mobilization) were linked to cone stage.
This is a comprehensive proteomic analysis of epithelial and stromal fractions in KC cone and non-cone regions. Our results have highlighted that KC stromal changes are related to the altered immunological complement systems. Alternatively, non-cone epithelial changes primarily involve metabolic disorders whereas additional immune deregulation and tissue degeneration are found in cone development.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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