{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:38:02Z","timestamp":1787027882999,"version":"build-2736575974"},"reference-count":105,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Fuchs\u2019 endothelial corneal dystrophy (FECD) is a progressive eye disease characterized by accelerated loss of endothelial cells and the development of focal excrescence (guttae) on Descemet\u2019s membrane, resulting in cornea opacity and vision deterioration. The development of FECD is assumed to be due to the interplay between genetic and environmental factor risks, causing abnormal extracellular-matrix organization, increased oxidative stress, apoptosis and unfolded protein response. However, the molecular knowledge of FECD is limited. The development of genome-wide platforms and bioinformatics approaches has enabled us to identify numerous genetic loci that are associated with FECD. In this review, we gathered genome-wide studies (n = 31) and sorted them according to genomics (n = 9), epigenomics (n = 3), transcriptomics (n = 15), proteomics (n = 3) and metabolomics (n = 1) levels to characterize progress in understanding FECD. We also extracted validated differentially expressed\/spliced genes and proteins identified through comparisons of FECD case and control groups. In addition, highlighted loci from each omics layer were combined according to a comparison with similar study groups from original studies for downstream gene-set enrichment analysis, which provided the most significant biological pathways related to extracellular-matrix organization. In the future, multiomics study approaches are needed to increase the sample size and statistical power to identify strong candidate genes for functional studies on animal models and cell lines for better understanding FECD.<\/jats:p>","DOI":"10.3390\/cimb47030135","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T11:03:37Z","timestamp":1740049417000},"page":"135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["How \u201cOmics\u201d Studies Contribute to a Better Understanding of Fuchs\u2019 Endothelial Corneal Dystrophy"],"prefix":"10.3390","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8532-9205","authenticated-orcid":false,"given":"Erika","family":"Pra\u0161nikar","sequence":"first","affiliation":[{"name":"Eye Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spela","family":"Stunf Pukl","sequence":"additional","affiliation":[{"name":"Eye Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.exer.2011.06.004","article-title":"Molecular mechanisms underlying the corneal endothelial pump","volume":"95","author":"Bonanno","year":"2012","journal-title":"Exp. Eye Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.jcrs.2010.12.037","article-title":"Anatomy and physiology of the cornea","volume":"37","author":"Delmonte","year":"2011","journal-title":"J. Cataract Refract. Surg."},{"key":"ref_3","unstructured":"Weisenthal, R.W., Daly, M.K., De Freitas, D., Feder, R.S., Orlin, S.E., Tu, E.Y., Van Meter, W.S., and Verdier, D.D. (2019). Structure and function of the external eye and cornea. 2020\u20132021 BCSC Section 8: External Disease and Cornea, American Academy of Ophthalmology."},{"key":"ref_4","first-page":"779","article-title":"Central corneal endothelial cell changes over a ten-year period","volume":"38","author":"Bourne","year":"1997","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"671","DOI":"10.3109\/02713688509017661","article-title":"Changes in the normal corneal endothelial cellular pattern as a function of age","volume":"4","author":"Yee","year":"1985","journal-title":"Curr. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100904","DOI":"10.1016\/j.preteyeres.2020.100904","article-title":"Corneal endothelial dysfunction: Evolving understanding and treatment options","volume":"82","author":"Price","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/s40123-022-00637-1","article-title":"Fuchs dystrophy and cataract: Diagnosis, evaluation and treatment","volume":"12","author":"Ali","year":"2023","journal-title":"Ophthalmol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1167\/iovs.13-13517","article-title":"Mitochondrial polymorphism A10398G and haplogroup I are associated with Fuchs\u2019 endothelial corneal dystrophy","volume":"55","author":"Li","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1073\/pnas.1912546116","article-title":"Ultraviolet A light induces DNA damage and estrogen-DNA adducts in Fuchs endothelial corneal dystrophy causing females to be more affected","volume":"117","author":"Liu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kumar, V., Deshpande, N., Parekh, M., Wong, R., Ashraf, S., Zahid, M., Hui, H., Miall, A., Kimpton, S., and Price, M.O. (2023). Estrogen genotoxicity causes preferential development of Fuchs endothelial corneal dystrophy in females. Redox Biol., 10.","DOI":"10.1016\/j.redox.2023.102986"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zwingelberg, S.B., Lautwein, B., Baar, T., Gutenbrunner, M.H., Von Brandenstein, M., Nobacht, S., Matthaei, M., and Bachmann, B.O. (2024). The influence of obesity, diabetes mellitus and smoking on fuchs endothelial corneal dystrophy (FECD). Sci. Rep., 14.","DOI":"10.1038\/s41598-024-61948-w"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.ajo.2009.09.009","article-title":"Unfolded protein response in Fuchs endothelial corneal dystrophy: A unifying pathogenic pathway?","volume":"149","author":"Engler","year":"2010","journal-title":"Am. J. Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1586\/eop.12.39","article-title":"The genetics of Fuchs\u2019 corneal dystrophy","volume":"7","author":"Iliff","year":"2012","journal-title":"Expert Rev. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.2353\/ajpath.2010.100279","article-title":"Evidence of oxidative stress in the pathogenesis of Fuchs endothelial corneal dystrophy","volume":"177","author":"Jurkunas","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.exer.2014.10.011","article-title":"Transcript profile of cellular senescence-related genes in Fuchs endothelial corneal dystrophy","volume":"129","author":"Matthaeia","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"M\u00e9thot, S.J., Proulx, S., Brunette, I., and Rochette, P.J. (2020). Chronology of cellular events related to mitochondrial burnout leading to cell death in Fuchs endothelial corneal dystrophy. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-62602-x"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100863","DOI":"10.1016\/j.preteyeres.2020.100863","article-title":"Fuchs endothelial corneal dystrophy: The vicious cycle of Fuchs pathogenesis","volume":"80","author":"Tone","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1159\/000063656","article-title":"Prevalence of primary cornea guttata and morphology of corneal endothelium in aging Japanese and Singaporean subjects","volume":"34","author":"Kitagawa","year":"2002","journal-title":"Ophthalmic Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.ophtha.2005.12.014","article-title":"Prevalence and risk factors for cornea guttata in the Reykjavik eye study","volume":"113","author":"Zoega","year":"2006","journal-title":"Ophthalmology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.ajo.2011.11.033","article-title":"Prevalence and severity of Fuchs corneal dystrophy in Tangier island","volume":"153","author":"Eghrari","year":"2012","journal-title":"Am. J. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Dai, X., and Shen, L. (2022). Advances and trends in omics technology development. Front. Med., 1.","DOI":"10.3389\/fmed.2022.911861"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/bioinformatics\/btp713","article-title":"Bioinformatics challenges for genome-wide association studies","volume":"26","author":"Moore","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Conesa, A., Madrigal, P., Tarazona, S., Gomez-cabrero, D., Cervera, A., Mcpherson, A., Szcze, W., Gaffney, D.J., Elo, L.L., and Zhang, X. (2016). A survey of best practices for RNA-seq data analysis. Genome Biol., 17.","DOI":"10.1186\/s13059-016-0881-8"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hasin, Y., Seldin, M., and Lusis, A. (2017). Multi-omics approaches to disease. Genome Biol., 18.","DOI":"10.1186\/s13059-017-1215-1"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"BIO88","DOI":"10.1167\/iovs.17-21809","article-title":"Den Omics biomarkers in ophthalmology","volume":"58","author":"Lauwen","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s10792-024-02994-1","article-title":"Fuchs endothelial corneal dystrophy: An updated review","volume":"44","author":"Altamirano","year":"2024","journal-title":"Int. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.4103\/ijo.IJO_992_22","article-title":"Update on the genetics of corneal endothelial dystrophies","volume":"70","author":"Kannabiran","year":"2022","journal-title":"Indian J. Ophthalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.exer.2014.10.023","article-title":"The pathophysiology of Fuchs\u2019 endothelial dystrophy\u2014A review of molecular and cellular insights","volume":"130","author":"Zhang","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1167\/iovs.04-0937","article-title":"Inheritance of a novel COL8A2 mutation defines a distinct early-onset subtype of Fuchs corneal dystrophy","volume":"46","author":"Gottsch","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1167\/iovs.05-0578","article-title":"Linkage of late-onset Fuchs corneal dystrophy to a novel locus at 13pTel-13q12.13","volume":"47","author":"Sundin","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3919","DOI":"10.1167\/iovs.05-1619","article-title":"A common locus for late-onset Fuchs corneal dystrophy maps to 18q21.2-q21.32","volume":"47","author":"Sundin","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5667","DOI":"10.1167\/iovs.09-3764","article-title":"Linkage of a mild late-onset phenotype of Fuchs corneal dystrophy to a novel locus at 5q33.1-q35.2","volume":"50","author":"Riazuddin","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1167\/iovs.08-1839","article-title":"Genome-wide linkage scan in Fuchs endothelial corneal dystrophy","volume":"50","author":"Afshari","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.ajhg.2013.08.010","article-title":"Mutations in AGBL1 cause dominant late-onset Fuchs corneal dystrophy and alter protein-protein interaction with TCF4","volume":"93","author":"Riazuddin","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1080\/13816810.2020.1759109","article-title":"A family of fuchs endothelial corneal dystrophy and anterior polar cataract with an analysis of whole exome sequencing","volume":"41","author":"Jiang","year":"2020","journal-title":"Ophthalmic Genet."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Petersen, B., Fredrich, B., Hoeppner, M.P., Ellinghaus, D., and Franke, A. (2017). Opportunities and challenges of whole-genome and -exome sequencing. BMC Genet., 18.","DOI":"10.1186\/s12863-017-0479-5"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1056\/NEJMoa1007064","article-title":"E2-2 protein and Fuchs\u2019s corneal dystrophy","volume":"363","author":"Baratz","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Li, Y., Minear, M.A., Rimmler, J., Zhao, B., Balajonda, E., Hauser, M.A., Allingham, R.R., Eghrari, A.O., Riazuddin, S.A., and Katsanis, N. (2011). Replication of TCF4 through association and linkage studies in late-onset Fuchs endothelial corneal dystrophy. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018044"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"14898","DOI":"10.1038\/ncomms14898","article-title":"Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy","volume":"30","author":"Afshari","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1093\/hmg\/10.21.2415","article-title":"Missense mutations in COL8A2, the gene encoding the \u03b12 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy","volume":"10","author":"Biswas","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Igo, R.P., Kopplin, L.J., Joseph, P., Truitt, B., Fondran, J., Bardenstein, D., Aldave, A.J., Croasdale, C.R., Price, M.O., and Rosenwasser, M. (2012). Differing roles for TCF4 and COL8A2 in central corneal thickness and Fuchs endothelial corneal dystrophy. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046742"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1620\/tjem.234.17","article-title":"Polymorphisms of the apoptosis-related FAS and FAS ligand genes in keratoconus and Fuchs endothelial corneal dystrophy","volume":"234","author":"Synowiec","year":"2014","journal-title":"Tohoku J. Exp. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1167\/iovs.13-12611","article-title":"Association and familial segregation of CTG18.1 trinucleotide repeat Expansion of TCF4 gene in Fuchs\u2019 endothelial corneal dystrophy","volume":"2","author":"Mootha","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.12659\/MSM.894273","article-title":"Variation in DNA base excision repair genes in Fuchs endothelial corneal dystrophy","volume":"21","author":"Polakowski","year":"2015","journal-title":"Med. Sci. Monit."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1097\/ICO.0000000000002183","article-title":"Coexistence of congenital hereditary endothelial dystrophy and Fuchs endothelial corneal dystrophy associated with SLC4A11 mutations in affected families","volume":"39","author":"Chaurasia","year":"2020","journal-title":"Cornea"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/aos.15032","article-title":"TCF4 trinucleotide repeat expansion in Swedish cases with Fuchs\u2019 endothelial corneal dystrophy","volume":"100","author":"Viberg","year":"2022","journal-title":"Acta Ophthalmol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Tsedilina, T.R., Sharova, E., Iakovets, V., and Skorodumova, O.L. (2023). Systematic review of SLC4A11, variants in the development of Fuchs\u2019 endothelial corneal dystrophy. Front. Med., 27.","DOI":"10.3389\/fmed.2023.1153122"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s10384-003-0063-6","article-title":"Analysis of COL8A2 gene mutation in Japanese patients with Fuchs\u2019 endothelial dystrophy and posterior polymorphous dystrophy","volume":"48","author":"Kobayashi","year":"2004","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Hemadevi, B., Srinivasan, M., Arunkumar, J., and Prajna, N.V. (2010). Genetic analysis of patients with Fuchs endothelial corneal dystrophy in India. BMC Ophthalmol., 10.","DOI":"10.1186\/1471-2415-10-3"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4865","DOI":"10.1167\/iovs.15-17082","article-title":"Trinucleotide repeat expansion in the TCF4 gene in Fuchs\u2019 endothelial corneal dystrophy in Japanese","volume":"56","author":"Nakano","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.3892\/ijmm.2016.2570","article-title":"Analysis of SLC4A11, ZEB1, LOXHD1, COL8A2 and TCF4 gene sequences in a multi-generational family with late-onset Fuchs corneal dystrophy","volume":"37","author":"Tang","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1080\/13816810.2018.1474367","article-title":"Analysis of candidate genes ZEB1 and LOXHD1 in late-onset Fuchs\u2019 endothelial corneal dystrophy in an Indian cohort","volume":"39","author":"Rao","year":"2018","journal-title":"Ophthalmic Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/cge.13368","article-title":"Further audiovestibular characterization of DFNB77, caused by deleterious variants in LOXHD1, and investigation into the involvement of Fuchs corneal dystrophy","volume":"94","author":"Wesdorp","year":"2018","journal-title":"Clin. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1097\/ICO.0000000000001952","article-title":"Association of rs613872 and trinucleotide repeat expansion in the TCF4 gene of German patients with Fuchs endothelial corneal dystrophy","volume":"38","author":"Okumura","year":"2019","journal-title":"Cornea"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"963","DOI":"10.21873\/invivo.11565","article-title":"TCF4 and COL8A2 gene polymorphism screening in a Greek population of late-onset Fuchs endothelial corneal dystrophy","volume":"33","author":"Moschos","year":"2019","journal-title":"In Vivo"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"32","DOI":"10.3109\/13816810.2012.726396","article-title":"Confirmation of the association between the TCF4 risk allele and Fuchs endothelial corneal dystrophy in patients from the Midwestern United States","volume":"34","author":"Stamler","year":"2013","journal-title":"Ophthalmic Genet."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kuot, A., Hewitt, A.W., Snibson, G.R., Souzeau, E., Mills, R., Craig, J.E., Burdon, K.P., and Sharma, S. (2017). TGC repeat expansion in the TCF4 gene increases the risk of Fuchs\u2019 endothelial corneal dystrophy in Australian cases. PLoS ONE, 23.","DOI":"10.1371\/journal.pone.0183719"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5573","DOI":"10.1167\/iovs.11-7568","article-title":"Association of TCF4 gene polymorphisms with Fuchs\u2019 corneal dystrophy in the Chinese","volume":"52","author":"Thalamuthu","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/s41433-019-0595-8","article-title":"Trinucleotide repeat expansion in the transcription factor 4 (TCF4) gene in Thai patients with Fuchs endothelial corneal dystrophy","volume":"34","author":"Okumura","year":"2020","journal-title":"Eye"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Wieben, E.D., Aleff, R.A., Tosakulwong, N., Butz, M.L., Highsmith, W.E., Edwards, A.O., and Baratz, K.H. (2012). A common trinucleotide repeat expansion within the transcription factor 4 (TCF4, E2-2) gene predicts Fuchs corneal dystrophy. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049083"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/ICO.0000000000001049","article-title":"CTG18.1 expansion in TCF4 increases likelihood of transplantation in Fuchs corneal dystrophy","volume":"36","author":"Eghrari","year":"2017","journal-title":"Cornea"},{"key":"ref_63","first-page":"rs-2762003","article-title":"Multi-ancestry GWAS of Fuchs corneal dystrophy highlights roles of laminins, collagen, and endothelial cell regulation","volume":"rs.3","author":"Peachey","year":"2023","journal-title":"Res. Sq."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.mrfmmm.2013.12.001","article-title":"Mutagenesis of mitochondrial DNA in Fuchs endothelial corneal dystrophy","volume":"760","author":"Czarny","year":"2014","journal-title":"Mutat. Res."},{"key":"ref_65","first-page":"1514","article-title":"Mitochondrial complex 1 gene analysis in keratoconus","volume":"17","author":"Pathak","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Kenney, M.C., Hertzog, D., Chak, G., Atilano, S.R., Khatibi, N., Soe, K., Nobe, A., Yang, E., Chwa, M., and Zhu, F. (2013). Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: A case control study. BMC Med. Genet., 14.","DOI":"10.1186\/1471-2350-14-4"},{"key":"ref_67","first-page":"1468","article-title":"Mitochondrial DNA lineages of African origin confer susceptibility to primary open-angle glaucoma in Saudi patients","volume":"3","author":"Osman","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"109403","DOI":"10.1016\/j.exer.2023.109403","article-title":"Intergenic variants, rs1200114 and rs1200108 are genetically associated along with a decreased ATP1B1 expression in Fuchs endothelial corneal dystrophy","volume":"228","author":"Chakraborty","year":"2023","journal-title":"Exp. Eye Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1097\/ICO.0000000000001521","article-title":"Identification of a novel TCF4 isoform in human corneal endothelium","volume":"37","author":"Eghrari","year":"2018","journal-title":"Cornea"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Bhattacharyya, N., Chai, N., Hafford-tear, N.J., Sadan, A.N., Szabo, A., Zarouchlioti, C., Jedlickova, J., Leung, S.K., Liao, T., and Dudakova, L. (2024). Deciphering novel TCF4 -driven mechanisms underlying a common triplet repeat expansion-mediated disease. PLoS Genet., 20.","DOI":"10.1371\/journal.pgen.1011230"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Zhang, X., Kumar, A., Sathe, A.A., Mootha, V.V., and Xing, C. (2023). Transcriptomic meta-analysis reveals ERR\u03b1-mediated oxidative phosphorylation is downregulated in Fuchs\u2019 endothelial corneal dystrophy. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0295542"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5979","DOI":"10.1074\/jbc.M114.621607","article-title":"RNA Toxicity and missplicing in the common eye disease Fuchs endothelial corneal dystrophy","volume":"290","author":"Du","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1167\/iovs.16-20900","article-title":"Trinucleotide repeat expansion in the transcription factor 4 (TCF4) gene leads to widespread mRNA splicing changes in Fuchs\u2019 endothelial corneal dystrophy","volume":"58","author":"Wieben","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Wieben, E.D., Aleff, R.A., Tang, X., Kalari, K.R., Maguire, L.J., Patel, V., Baratz, K.H., and Fautsch, M.P. (2018). Gene expression in the corneal endothelium of Fuchs endothelial corneal dystrophy patients with and without expansion of a trinucleotide repeat in TCF4. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200005"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"6740","DOI":"10.1093\/nar\/gkaa422","article-title":"Analyzing pre-symptomatic tissue to gain insights into the molecular and mechanistic origins of late-onset degenerative trinucleotide repeat disease","volume":"48","author":"Chu","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"108692","DOI":"10.1016\/j.exer.2021.108692","article-title":"Differential gene expression analysis of corneal endothelium indicates involvement of phagocytic activity in Fuchs\u2019 endothelial corneal dystrophy","volume":"210","author":"Kuot","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"109712","DOI":"10.1016\/j.exer.2023.109712","article-title":"Integrative analysis of gene expression datasets in corneal endothelium samples of Fuchs endothelial corneal dystrophy","volume":"237","author":"Zhang","year":"2023","journal-title":"Exp. Eye Res."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Nakagawa, T., Tokuda, Y., Nakano, M., Komori, Y., Hanada, N., Tourtas, T., Schrehardt, U.S., Kruse, F., Tashiro, K., and Koizumi, N. (2023). RNA-Seq\u2013based transcriptome analysis of corneal endothelial cells derived from patients with Fuchs endothelial corneal dystrophy. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-35468-y"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"104047","DOI":"10.1016\/j.dib.2019.104047","article-title":"Dataset on transcriptome profiling of corneal endothelium from patients with Fuchs endothelial corneal dystrophy","volume":"25","author":"Nikitina","year":"2019","journal-title":"Data Brief"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Liu, C., Gao, Z., Li, J., and Zhou, Q. (2022). Identification of novel therapeutic targets for Fuchs\u2019 endothelial corneal dystrophy based on gene bioinformatics analysis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0264018"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1167\/iovs.16-20880","article-title":"Identification of circulating fibrocytes and dendritic derivatives in corneal endothelium of patients with Fuchs\u2019 dystrophy","volume":"58","author":"Wouters","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1097\/ICO.0000000000001212","article-title":"Immunohistochemical profiling of corneas with Fuchs endothelial corneal dystrophy","volume":"36","author":"Janssens","year":"2017","journal-title":"Cornea"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Cui, Z., Zeng, Q., Guo, Y., Liu, S., Wang, P., Xie, M., and Chen, J. (2018). Pathological molecular mechanism of symptomatic late-onset Fuchs endothelial corneal dystrophy by bioinformatic analysis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197750"},{"key":"ref_84","first-page":"5580595","article-title":"Incorporating differential gene expression analysis with predictive biomarkers to identify novel therapeutic drugs for Fuchs endothelial corneal dystrophy","volume":"28","author":"Wen","year":"2021","journal-title":"J. Ophthalmol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1167\/iovs.65.6.27","article-title":"Dysregulation of the TCF4 isoform in corneal endothelial cells of patients with Fuchs endothelial corneal dystrophy","volume":"65","author":"Honda","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.omtn.2022.01.005","article-title":"Heterogeneity of human corneal endothelium implicates lncRNA NEAT1 in Fuchs endothelial corneal dystrophy","volume":"27","author":"Wang","year":"2022","journal-title":"Mol. Ther. Nucleic Acid"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Clough, E., and Barrett, T. (2016). The Gene Expression Omnibus database. Statistical Genomics, Humana. Methods in Molecular Biology.","DOI":"10.1007\/978-1-4939-3578-9_5"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.cell.2017.05.045","article-title":"Dynamic RNA modifications in gene expression regulation","volume":"169","author":"Roundtree","year":"2017","journal-title":"Cell"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Pukl Stunf, S. (2022). MicroRNA of epithelial to mesenchymal transition in Fuchs\u2019 endothelial corneal dystrophy. Genes, 13.","DOI":"10.3390\/genes13101711"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1167\/iovs.13-12689","article-title":"Endothelial cell microRNA expression in human late-onset Fuchs\u2019 dystrophy","volume":"55","author":"Matthaei","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Khuc, E., Bainer, R., Wolf, M., Clay, S.M., Weisenberger, D.J., Kemmer, J., Weaver, V.M., Hwang, D.G., and Chan, M.F. (2017). Comprehensive characterization of DNA methylation changes in Fuchs endothelial corneal dystrophy. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0175112"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Pan, P., Weisenberger, D.J., Zheng, S., Wolf, M., Hwang, D.G., Rose-nussbaumer, J.R., Jurkunas, U.V., and Chan, M.F. (2019). Aberrant DNA methylation of miRNAs in Fuchs endothelial corneal dystrophy. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-52727-z"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/s00018-023-04714-x","article-title":"DNA methylation changes and increased mRNA expression of coagulation proteins, factor V and thrombomodulin in Fuchs endothelial corneal dystrophy","volume":"80","author":"Westin","year":"2023","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1167\/iovs.17-23265","article-title":"Repeat-associated non-ATG (RAN) translation in Fuchs\u2019 endothelial corneal dystrophy","volume":"59","author":"Soragni","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_95","first-page":"2376","article-title":"Alterations in the aqueous humor proteome in patients with Fuchs endothelial corneal dystrophy","volume":"11","author":"Richardson","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1111\/ceo.13569","article-title":"Reduced expression of apolipoprotein E and immunoglobulin heavy constant gamma 1 proteins in Fuchs endothelial corneal dystrophy","volume":"47","author":"Kuot","year":"2019","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Nakagawa, T., Okumura, N., Ikegawa, M., Toyama, Y., Nirasawa, T., Mascarelli, F., Vaitinadapoule, H., Aouimeur, I., He, Z., and Gain, P. (2023). Shotgun proteomics identification of proteins expressed in the Descemet\u2019 s membrane of patients with Fuchs endothelial corneal dystrophy. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-37104-1"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1111\/aos.13374","article-title":"Changes in lipidomic profile of aqueous humour in Fuchs endothelial dystrophy","volume":"95","author":"Cabrerizo","year":"2017","journal-title":"Acta Ophthalmol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/0002-9394(86)90526-X","article-title":"Aqueous amino acid levels in Fuchs\u2019 corneal dystrophy","volume":"102","author":"Rosenthal","year":"1986","journal-title":"Am. J. Ophthalmol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_101","first-page":"1049","article-title":"Awareness and attitudes toward corneal donation: Challenges and opportunities","volume":"7","author":"Muir","year":"2018","journal-title":"Clin. Ophthalmol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.ophtha.2020.09.002","article-title":"Five-year follow-up of first 11 patients undergoing injection of cultured corneal endothelial cells for corneal endothelial failure","volume":"128","author":"Numa","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.exer.2014.06.002","article-title":"N-Acetylcysteine increases corneal endothelial cell survival in a mouse model of Fuchs endothelial corneal dystrophy","volume":"127","author":"Kim","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.chembiol.2020.10.007","article-title":"A small molecule that binds an RNA repeat expansion stimulates its decay via the exosome complex","volume":"28","author":"Angelbello","year":"2021","journal-title":"Cell Chem. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1089\/nat.2019.0838","article-title":"Delivery of antisense oligonucleotides to the cornea","volume":"30","author":"Chau","year":"2020","journal-title":"Nucleic Acid Ther."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/3\/135\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:39:03Z","timestamp":1760027943000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/3\/135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,20]]},"references-count":105,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["cimb47030135"],"URL":"https:\/\/doi.org\/10.3390\/cimb47030135","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,20]]}}}