{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T14:01:21Z","timestamp":1769090481026,"version":"3.49.0"},"reference-count":50,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T00:00:00Z","timestamp":1697673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea","award":["NRF-2021R1A2C4001596"],"award-info":[{"award-number":["NRF-2021R1A2C4001596"]}]},{"name":"National Research Foundation of Korea","award":["6-2021-0117"],"award-info":[{"award-number":["6-2021-0117"]}]},{"name":"Yonsei University College of Medicine","award":["NRF-2021R1A2C4001596"],"award-info":[{"award-number":["NRF-2021R1A2C4001596"]}]},{"name":"Yonsei University College of Medicine","award":["6-2021-0117"],"award-info":[{"award-number":["6-2021-0117"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Earlier studies have reported that elevated protein levels in the aqueous humor (AH) are associated with corneal endothelial cell dysfunction (CECD), but the details of the underlying mechanism as well as specific biomarkers for CECD remain elusive. In the present study, we aimed to identify protein markers in AH directly associated with changes to corneal endothelial cells (CECs), as AH can be easily obtained for analysis. We carried out an in-depth proteomic analysis of patient-derived AH as well as transcriptomic analysis of CECs from the same patients with bullous keratopathy (BK) resulting from CECD. We first determined differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) from CECs and AH in CECD, respectively. By combining transcriptomic and proteomic analyses, 13 shared upregulated markers and 22 shared downregulated markers were observed between DEGs and DEPs. Among these 35 candidates from biomarker profiling, three upregulated markers were finally verified via data-independent acquisition (DIA) proteomic analysis using additional individual AH samples, namely metallopeptidase inhibitor 1 (TIMP1), Fc fragment of IgG binding protein (FCGBP), and angiopoietin-related protein 7 (ANGPTL7). Furthermore, we confirmed these AH biomarkers for CECD using individual immunoassay validation. Conclusively, our findings may provide valuable insights into the disease process and identify biofluid markers for the assessment of CEC function during BK development.<\/jats:p>","DOI":"10.3390\/ijms242015354","type":"journal-article","created":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T05:43:28Z","timestamp":1697694208000},"page":"15354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Integrated Analysis of Transcriptome and Proteome of the Human Cornea and Aqueous Humor Reveal Novel Biomarkers for Corneal Endothelial Cell Dysfunction"],"prefix":"10.3390","volume":"24","author":[{"given":"Chae-Eun","family":"Moon","sequence":"first","affiliation":[{"name":"Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"},{"name":"Department of Ophthalmology, Yongin Severance Hospital, Yongin 16995, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Hun","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yongin 17104, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Joo","family":"Cho","sequence":"additional","affiliation":[{"name":"The Yonsei Eye Clinic, Seoul 06289, Republic of Korea"},{"name":"Department of Ophthalmology, HanGil Eye Hospital, Incheon 21388, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kee Yong","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, HanGil Eye Hospital, Incheon 21388, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyusun","family":"Han","sequence":"additional","affiliation":[{"name":"Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9855-1980","authenticated-orcid":false,"given":"Kyoung Yul","family":"Seo","sequence":"additional","affiliation":[{"name":"Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1123-2136","authenticated-orcid":false,"given":"Hyung Keun","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"},{"name":"Department of Ophthalmology, Gangnam Severance Hospital, Seoul 06273, Republic of Korea"},{"name":"College of Pharmacy, Yonsei University, Incheon 21983, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7211-6278","authenticated-orcid":false,"given":"Yong Woo","family":"Ji","sequence":"additional","affiliation":[{"name":"Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea"},{"name":"Department of Ophthalmology, Yongin Severance Hospital, Yongin 16995, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S1350-9462(02)00065-4","article-title":"Proliferative capacity of the corneal endothelium","volume":"22","author":"Joyce","year":"2003","journal-title":"Prog. 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