Mapping Keratoconus Molecular Substrates by Multiplexed High-Resolution Proteomics of Unpooled Corneas Article Swipe
Vishal Shinde
,
Nan Hu
,
Santosh Renuse
,
Alka Mahale
,
Akhilesh Pandey
,
Charles G. Eberhart
,
Donald U. Stone
,
Samar A. Al-Swailem
,
Azza Maktabi
,
Shukti Chakravarti
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1089/omi.2019.0143
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1089/omi.2019.0143
Keratoconus (KCN) is a leading cause for cornea grafting worldwide. Keratoconus is a multifactorial disease that causes progressive thinning of the cornea and whose etiology is poorly understood. Several studies have used proteomics on patient tear fluids to identify potential biomarkers. However, proteome of the cornea itself has not been investigated fully. We report here new findings from a case–control study using multiplexed mass spectrometry (MS) on individual (unpooled) corneas to gain deeper insights into proteins and biomarkers relevant to keratoconus. We employed a high-pressure approach to extract total protein from individual corneas from five cases and five controls, followed by trypsin digestion and tandem mass tag (TMT) labeling. The MS-derived data were searched using the Human NCBI RefSeq protein database v92, with peptides and proteins filtered at 1% false discovery rate. A total of 3132 proteins were detected, of which 627 were altered significantly ( p ≤ 0.05) in keratoconus corneas. The increases were overwhelmingly in the mTOR/PI3/AKT signal-mediated regulations of cell survival and proliferation, nonsense-mediated decay of transcripts, and proteasomal pathways. The decreases were in several extracellular matrix proteins and in many members of the complement system. Importantly, this multiplexed proteomic study of keratoconus corneas identified, to our knowledge, the largest number of corneal proteins. The novel findings include changes in pathways that regulate transcript stability, proteasomal degradation, and the complement system in corneas with keratoconus. These observations offer new prospects toward future discovery of novel molecular targets for diagnostic and therapeutic innovations for patients with keratoconus.
Related Topics
Concepts
Keratoconus
Proteomics
Proteome
Cornea
Quantitative proteomics
Chemistry
Biology
Medicine
Bioinformatics
Biochemistry
Ophthalmology
Gene
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1089/omi.2019.0143
- OA Status
- green
- Cited By
- 29
- References
- 65
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2982151747
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2982151747Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1089/omi.2019.0143Digital Object Identifier
- Title
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Mapping Keratoconus Molecular Substrates by Multiplexed High-Resolution Proteomics of Unpooled CorneasWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-10-25Full publication date if available
- Authors
-
Vishal Shinde, Nan Hu, Santosh Renuse, Alka Mahale, Akhilesh Pandey, Charles G. Eberhart, Donald U. Stone, Samar A. Al-Swailem, Azza Maktabi, Shukti ChakravartiList of authors in order
- Landing page
-
https://doi.org/10.1089/omi.2019.0143Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
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greenOpen access status per OpenAlex
- OA URL
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https://www.ncbi.nlm.nih.gov/pmc/articles/6857467Direct OA link when available
- Concepts
-
Keratoconus, Proteomics, Proteome, Cornea, Quantitative proteomics, Chemistry, Biology, Medicine, Bioinformatics, Biochemistry, Ophthalmology, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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29Total citation count in OpenAlex
- Citations by year (recent)
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2025: 8, 2024: 3, 2023: 6, 2022: 3, 2021: 3Per-year citation counts (last 5 years)
- References (count)
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65Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.understood. | 28 |
| abstract_inverted_index.Importantly, | 190 |
| abstract_inverted_index.degradation, | 220 |
| abstract_inverted_index.investigated | 51 |
| abstract_inverted_index.keratoconus. | 81, 228, 249 |
| abstract_inverted_index.mTOR/PI3/AKT | 159 |
| abstract_inverted_index.observations | 230 |
| abstract_inverted_index.spectrometry | 65 |
| abstract_inverted_index.transcripts, | 170 |
| abstract_inverted_index.extracellular | 179 |
| abstract_inverted_index.high-pressure | 85 |
| abstract_inverted_index.significantly | 145 |
| abstract_inverted_index.case–control | 60 |
| abstract_inverted_index.multifactorial | 14 |
| abstract_inverted_index.overwhelmingly | 156 |
| abstract_inverted_index.proliferation, | 166 |
| abstract_inverted_index.signal-mediated | 160 |
| abstract_inverted_index.nonsense-mediated | 167 |
| cited_by_percentile_year.max | 99 |
| cited_by_percentile_year.min | 95 |
| corresponding_author_ids | https://openalex.org/A5058974651 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 10 |
| corresponding_institution_ids | https://openalex.org/I4210086933 |
| citation_normalized_percentile.value | 0.86947967 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |