Differential epithelial and stromal protein profiles in cone and non-cone regions of keratoconus corneas
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2019
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| Online Access: | https://hdl.handle.net/10356/85860 http://hdl.handle.net/10220/48250 |
| _version_ | 1826129582051295232 |
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| author | Yam, Gary Hin-Fai Fuest, Matthias Zhou, Lei Liu, Yu-Chi Deng, Lu Chan, Anita Sook-Yee Ong, Hon Shing Khor, Wei-Boon Ang, Marcus Mehta, Jodhbir Singh |
| author2 | School of Materials Science & Engineering |
| author_facet | School of Materials Science & Engineering Yam, Gary Hin-Fai Fuest, Matthias Zhou, Lei Liu, Yu-Chi Deng, Lu Chan, Anita Sook-Yee Ong, Hon Shing Khor, Wei-Boon Ang, Marcus Mehta, Jodhbir Singh |
| author_sort | Yam, Gary Hin-Fai |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T07:42:54Z |
| format | Journal Article |
| id | ntu-10356/85860 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:42:54Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/858602023-07-14T15:57:21Z Differential epithelial and stromal protein profiles in cone and non-cone regions of keratoconus corneas Yam, Gary Hin-Fai Fuest, Matthias Zhou, Lei Liu, Yu-Chi Deng, Lu Chan, Anita Sook-Yee Ong, Hon Shing Khor, Wei-Boon Ang, Marcus Mehta, Jodhbir Singh School of Materials Science & Engineering DRNTU::Engineering::Materials Proteome Informatics Corneal Diseases 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. NRF (Natl Research Foundation, S’pore) NMRC (Natl Medical Research Council, S’pore) MOH (Min. of Health, S’pore) Published version 2019-05-17T02:59:11Z 2019-12-06T16:11:30Z 2019-05-17T02:59:11Z 2019-12-06T16:11:30Z 2019 Journal Article Yam, G. H.-F., Fuest, M., Zhou, L., Liu, Y.-C., Deng, L., Chan, A. S.-Y., . . . Mehta, J. S. (2019). Differential epithelial and stromal protein profiles in cone and non-cone regions of keratoconus corneas. Scientific Reports, 9, 2965-. doi:10.1038/s41598-019-39182-6 https://hdl.handle.net/10356/85860 http://hdl.handle.net/10220/48250 10.1038/s41598-019-39182-6 en Scientific Reports © 2019 The Author(s) (Nature Publishing Group). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. 17 p. application/pdf |
| spellingShingle | DRNTU::Engineering::Materials Proteome Informatics Corneal Diseases Yam, Gary Hin-Fai Fuest, Matthias Zhou, Lei Liu, Yu-Chi Deng, Lu Chan, Anita Sook-Yee Ong, Hon Shing Khor, Wei-Boon Ang, Marcus Mehta, Jodhbir Singh Differential epithelial and stromal protein profiles in cone and non-cone regions of keratoconus corneas |
| title | Differential epithelial and stromal protein profiles in cone and non-cone regions of keratoconus corneas |
| title_full | Differential epithelial and stromal protein profiles in cone and non-cone regions of keratoconus corneas |
| title_fullStr | Differential epithelial and stromal protein profiles in cone and non-cone regions of keratoconus corneas |
| title_full_unstemmed | Differential epithelial and stromal protein profiles in cone and non-cone regions of keratoconus corneas |
| title_short | Differential epithelial and stromal protein profiles in cone and non-cone regions of keratoconus corneas |
| title_sort | differential epithelial and stromal protein profiles in cone and non cone regions of keratoconus corneas |
| topic | DRNTU::Engineering::Materials Proteome Informatics Corneal Diseases |
| url | https://hdl.handle.net/10356/85860 http://hdl.handle.net/10220/48250 |
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