{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:33:28Z","timestamp":1787027608090,"version":"build-2736575974"},"reference-count":85,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR 2240"],"award-info":[{"award-number":["FOR 2240"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU COST","award":["CA18116"],"award-info":[{"award-number":["CA18116"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>The cornea is frequently exposed to ultraviolet (UV) radiation and absorbs a portion of this radiation. UVB in particular is absorbed by the cornea and will principally damage the topmost layer of the cornea, the epithelium. Epidemiological research shows that the UV damage of DNA is a contributing factor to corneal diseases such as pterygium. There are two main DNA photolesions of UV: cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6\u20134) photoproducts (6-4PPs). Both involve the abnormal linking of adjacent pyrimide bases. In particular, CPD lesions, which account for the vast majority of UV-induced lesions, are inefficiently repaired by nucleotide excision repair (NER) and are thus mutagenic and linked to cancer development in humans. Here, we apply two exogenous enzymes: CPD photolyase (CPDPL) and T4 endonuclease V (T4N5). The efficacy of these enzymes was assayed by the proteomic and immunofluorescence measurements of UVB-induced CPDs before and after treatment. The results showed that CPDs can be rapidly repaired by T4N5 in cell cultures. The usage of CPDPL and T4N5 in ex vivo eyes revealed that CPD lesions persist in the corneal limbus. The proteomic analysis of the T4N5-treated cells shows increases in the components of the angiogenic and inflammatory systems. We conclude that T4N5 and CPDPL show great promise in the treatment of CPD lesions, but the complete clearance of CPDs from the limbus remains a challenge.<\/jats:p>","DOI":"10.3390\/biology12020265","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T02:29:08Z","timestamp":1675823348000},"page":"265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Short-Term UVB Irradiation Leads to Persistent DNA Damage in Limbal Epithelial Stem Cells, Partially Reversed by DNA Repairing Enzymes"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3519-1359","authenticated-orcid":false,"given":"Thomas","family":"Volatier","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 62, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6097-5238","authenticated-orcid":false,"given":"Bj\u00f6rn","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Cologne Excellence Cluster for Cellular Stress Responses, Aging-Associated Diseases (CECAD) and Center for Molecular Medicine (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany"},{"name":"Institute for Genome Stability in Aging and Disease, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berbang","family":"Meshko","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 62, 50937 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Hadrian","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 62, 50937 Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 21, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1958-411X","authenticated-orcid":false,"given":"Claus","family":"Cursiefen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 62, 50937 Cologne, Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, 21, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Notara","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 62, 50937 Cologne, Germany"},{"name":"Cologne Excellence Cluster for Cellular Stress Responses, Aging-Associated Diseases (CECAD) and Center for Molecular Medicine (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1167\/iovs.05-1129","article-title":"Expression and regulation of cornified envelope proteins in human corneal epithelium","volume":"47","author":"Tong","year":"2006","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S1350-9462(01)00008-8","article-title":"The corneal wound healing response: Cytokine-mediated interaction of the epithelium, stroma, and inflammatory cells","volume":"20","author":"Wilson","year":"2001","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s00441-014-2032-4","article-title":"Roles of limbal microvascular net and limbal stroma in regulating maintenance of limbal epithelial stem cells","volume":"359","author":"Huang","year":"2015","journal-title":"Cell Tissue Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1367-0484(02)00054-1","article-title":"The limbal vasculature","volume":"26","author":"Papas","year":"2003","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/eye.1994.42","article-title":"Stem cells and corneal epithelial regeneration","volume":"8","author":"Kruse","year":"1994","journal-title":"Eye"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/eye.1994.41","article-title":"Perpetuation of stem cells in the eye","volume":"8","author":"Zieske","year":"1994","journal-title":"Eye"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"391","DOI":"10.4252\/wjsc.v6.i4.391","article-title":"Limbal stem cells: Central concepts of corneal epithelial homeostasis","volume":"6","author":"Yoon","year":"2014","journal-title":"World J. Stem Cells"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"12564","DOI":"10.1038\/s41598-018-30021-8","article-title":"UV light-blocking contact lenses protect against short-term UVB-induced limbal stem cell niche damage and inflammation","volume":"8","author":"Notara","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_9","first-page":"5622","article-title":"Effects of UVB irradiation on limbal stem cell niche and its role in cornea lymphangiogenesis","volume":"56","author":"Notara","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1167\/iovs.15-18343","article-title":"Short-Term Ultraviolet A Irradiation Leads to Dysfunction of the Limbal Niche Cells and an Antilymphangiogenic and Anti-inflammatory Micromilieu","volume":"57","author":"Notara","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_11","first-page":"4343","article-title":"Avastin effects on human limbal epithelial cell function and phenotype in vitro","volume":"57","author":"Notara","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12331","DOI":"10.1038\/s41598-019-48811-z","article-title":"Application of corneal injury models in dual fluorescent reporter transgenic mice to understand the roles of the cornea and limbus in angiogenic and lymphangiogenic privilege","volume":"9","author":"Gao","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_13","first-page":"264","article-title":"Corneal angiogenic privilege: Angiogenic and antiangiogenic factors in corneal avascularity, vasculogenesis, and wound healing (an American Ophthalmological Society thesis)","volume":"104","author":"Azar","year":"2006","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"108068","DOI":"10.1016\/j.exer.2020.108068","article-title":"12. Endothelial pump and barrier function","volume":"198","author":"Klyce","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.preteyeres.2015.07.002","article-title":"Progress in corneal wound healing","volume":"49","author":"Ljubimov","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1751-1097.1993.tb02273.x","article-title":"Distribution and repair of photolesions in DNA: Genetic consequences and the role of sequence context","volume":"57","author":"Sage","year":"1993","journal-title":"Photochem. Photobiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1562\/2004-12-01-RA-390","article-title":"Pyrimidine (6-4) pyrimidone photoproduct mapping after sublethal UVC doses: Nucleotide resolution using terminal transferase-dependent PCR","volume":"82","author":"Rochette","year":"2006","journal-title":"Photochem. Photobiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14831","DOI":"10.1073\/pnas.1110927108","article-title":"Dynamics and mechanism of cyclobutane pyrimidine dimer repair by DNA photolyase","volume":"108","author":"Liu","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"32950","DOI":"10.1074\/jbc.M404536200","article-title":"Investigation of the cyclobutane pyrimidine dimer (CPD) photolyase DNA recognition mechanism by NMR analyses","volume":"279","author":"Torizawa","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0027-5107(94)90037-X","article-title":"Induction of tandem-base change mutations","volume":"309","author":"Hutchinson","year":"1994","journal-title":"Mutat. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4173","DOI":"10.1021\/acs.biochem.6b00361","article-title":"Functional Conversion of CPD and (6-4) Photolyases by Mutation","volume":"55","author":"Yamada","year":"2016","journal-title":"Biochemistry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1126\/science.1101598","article-title":"Crystal structure of a photolyase bound to a CPD-like DNA lesion after in situ repair","volume":"306","author":"Mees","year":"2004","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1111\/j.1751-1097.1989.tb05578.x","article-title":"The biology of the (6-4) photoproduct","volume":"49","author":"Mitchell","year":"1989","journal-title":"Photochem. Photobiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Boros, G., Miko, E., Muramatsu, H., Weissman, D., Emri, E., van der Horst, G.T., Szegedi, A., Horkay, I., Emri, G., and Kariko, K. (2015). Identification of Cyclobutane Pyrimidine Dimer-Responsive Genes Using UVB-Irradiated Human Keratinocytes Transfected with In Vitro-Synthesized Photolyase mRNA. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131141"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/978-1-4939-3625-0_14","article-title":"Transfection of Human Keratinocytes with Nucleoside-Modified mRNA Encoding CPD-Photolyase to Repair DNA Damage","volume":"1428","author":"Boros","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0921-8777(97)00032-3","article-title":"Characterization of a human homolog of (6-4) photolyase","volume":"384","author":"Todo","year":"1997","journal-title":"Mutat. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4389","DOI":"10.1073\/pnas.90.10.4389","article-title":"Evidence for lack of DNA photoreactivating enzyme in humans","volume":"90","author":"Li","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1006\/geno.1996.0539","article-title":"Cloning, tissue expression, and mapping of a human photolyase homolog with similarity to plant blue-light receptors","volume":"37","author":"Kobayashi","year":"1996","journal-title":"Genomics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2868","DOI":"10.1016\/j.celrep.2017.02.066","article-title":"Major Roles for Pyrimidine Dimers, Nucleotide Excision Repair, and ATR in the Alternative Splicing Response to UV Irradiation","volume":"18","author":"Munoz","year":"2017","journal-title":"Cell Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mrfmmm.2006.06.008","article-title":"Nucleotide excision repair phenotype of human acute myeloid leukemia cell lines at various stages of differentiation","volume":"614","author":"Hsu","year":"2007","journal-title":"Mutat. Res. Mol. Mech. Mutagen."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrm3822","article-title":"Understanding nucleotide excision repair and its roles in cancer and ageing","volume":"15","author":"Marteijn","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s40123-019-00225-w","article-title":"Management Issues in Conjunctival Tumours: Ocular Surface Squamous Neoplasia","volume":"9","author":"Cohen","year":"2020","journal-title":"Ophthalmol. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1136\/bjophthalmol-2019-314650","article-title":"Epidemiology of invasive ocular surface squamous neoplasia in Canada during 1992\u20132010","volume":"104","author":"Darwich","year":"2020","journal-title":"Br. J. Ophthalmol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1159\/000509578","article-title":"Role of Conjunctival Ultraviolet Autofluorescence in Ocular Surface Squamous Neoplasia","volume":"6","author":"Yadav","year":"2020","journal-title":"Ocul. Oncol. Pathol."},{"key":"ref_35","first-page":"1620","article-title":"Bilateral ocular surface squamous neoplasia: A study of 25 patients and review of literature","volume":"32","author":"Vempuluru","year":"2021","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1136\/bjo.85.9.1080","article-title":"Quantification of the ultraviolet radiation (UVR) field in the human eye in vivo using novel instrumentation and the potential benefits of UVR blocking hydrogel contact lens","volume":"85","author":"Walsh","year":"2001","journal-title":"Br. J. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/j.ophtha.2012.02.049","article-title":"Clinicopathologic correlation of ocular surface squamous neoplasms at Bascom Palmer Eye Institute: 2001 to 2010","volume":"119","author":"Kao","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_38","first-page":"567","article-title":"Molecular Basis of Pterygium Development","volume":"31","author":"Zavala","year":"2016","journal-title":"Semin. Ophthalmol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1073\/pnas.67.4.1839","article-title":"T4 endonuclease involved in repair of DNA","volume":"67","author":"Yasuda","year":"1970","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0027-5107(02)00215-4","article-title":"Enhanced DNA repair of cyclobutane pyrimidine dimers changes the biological response to UV-B radiation","volume":"509","author":"Yarosh","year":"2002","journal-title":"Mutat. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1111\/1523-1747.ep12395551","article-title":"Localization of liposomes containing a DNA repair enzyme in murine skin","volume":"103","author":"Yarosh","year":"1994","journal-title":"J. Investig. Dermatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/S0140-6736(00)04214-8","article-title":"Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: A randomised study. Xeroderma Pigmentosum Study Group","volume":"357","author":"Yarosh","year":"2001","journal-title":"Lancet"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1517\/14712598.8.6.829","article-title":"T4 endonuclease V: Review and application to dermatology","volume":"8","author":"Cafardi","year":"2008","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_44","first-page":"405","article-title":"Repairing DNA damage in xeroderma pigmentosum: T4N5 lotion and gene therapy","volume":"7","author":"Zahid","year":"2008","journal-title":"J. Drugs Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1007\/s13555-020-00425-4","article-title":"Management Pearls on the Treatment of Actinic Keratoses and Field Cancerization","volume":"10","author":"Gilaberte","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Gomes, C., Silva, A.C., Marques, A.C., Lobo, J.S., and Amaral, M.H. (2020). Biotechnology Applied to Cosmetics and Aesthetic Medicines. Cosmetics, 7.","DOI":"10.3390\/cosmetics7020033"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E410","DOI":"10.1111\/jdv.14209","article-title":"Management of cancerization field with a medical device containing photolyase: A randomized, double-blind, parallel-group pilot study","volume":"31","author":"Moscarella","year":"2017","journal-title":"J. Eur. Acad. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s13555-019-0294-1","article-title":"Review of Clinical Evidence over 10 Years on Prevention and Treatment of a Film-Forming Medical Device Containing Photolyase in the Management of Field Cancerization in Actinic Keratosis","volume":"9","author":"Puig","year":"2019","journal-title":"Dermatol. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1111\/bjd.14721","article-title":"A 9-month, randomized, assessor-blinded, parallel-group study to evaluate clinical effects of film-forming medical devices containing photolyase and sun filters in the treatment of field cancerization compared with sunscreen in patients after successful photodynamic therapy for actinic keratosis","volume":"175","author":"Eibenschutz","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S1011-1344(01)00246-9","article-title":"Effect of xenogenic repair enzymes on photoimmunology and photocarcinogenesis","volume":"65","author":"Stege","year":"2001","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1073\/pnas.030528897","article-title":"Enzyme plus light therapy to repair DNA damage in ultraviolet-B-irradiated human skin","volume":"97","author":"Stege","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","first-page":"4227","article-title":"Pyrimidine dimer removal enhanced by DNA repair liposomes reduces the incidence of UV skin cancer in mice","volume":"52","author":"Yarosh","year":"1992","journal-title":"Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/j.1600-0781.1996.tb00188.x","article-title":"Enzyme therapy of xeroderma pigmentosum: Safety and efficacy testing of T4N5 liposome lotion containing a prokaryotic DNA repair enzyme","volume":"12","author":"Yarosh","year":"1996","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2958","DOI":"10.1073\/pnas.74.7.2958","article-title":"Specific action of T4 endonuclease V on damaged DNA in xeroderma pigmentosum cells in vivo","volume":"74","author":"Tanaka","year":"1977","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"23171","DOI":"10.1074\/jbc.M113.473173","article-title":"Identification of PDCL3 as a Novel Chaperone Protein Involved in the Generation of Functional VEGF Receptor 2","volume":"288","author":"Srinivasan","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"eaav5183","DOI":"10.1126\/scisignal.aav5183","article-title":"Specificity, versatility, and control of TGF-beta family signaling","volume":"12","author":"Derynck","year":"2019","journal-title":"Sci. Signal."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.jtos.2020.10.006","article-title":"Corneal stromal wound healing: Major regulators and therapeutic targets","volume":"19","author":"Kamil","year":"2021","journal-title":"Ocul. Surf."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7632","DOI":"10.1073\/pnas.92.17.7632","article-title":"Cloning and Characterization of a Human Type-Ii Receptor for Bone Morphogenetic Proteins","volume":"92","author":"Rosenzweig","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","first-page":"2626","article-title":"Bone morphogenic proteins 2 and 4 and their receptors in the adult human cornea","volume":"39","author":"Mohan","year":"1998","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1006\/dbio.2002.0793","article-title":"Adult corneal limbal epithelium: A model for studying neural potential of non-neural stem cells\/progenitors","volume":"250","author":"Zhao","year":"2002","journal-title":"Dev. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Sircoulomb, F., Bekhouche, I., Finetti, P., Adelaide, J., Ben Hamida, A., Bonansea, J., Raynaud, S., Innocenti, C., Charafe-Jauffret, E., and Tarpin, C. (2010). Genome profiling of ERBB2-amplified breast cancers. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-539"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4277","DOI":"10.1167\/iovs.04-0119","article-title":"Role of ErbB2 in corneal epithelial wound healing","volume":"45","author":"Xu","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1089\/jir.2015.0179","article-title":"Chromatin Landscape of the IRF Genes and Role of the Epigenetic Reader BRD4","volume":"36","author":"Bachu","year":"2016","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"13","DOI":"10.4161\/trns.22542","article-title":"Two faces of brd4: Mitotic bookmark and transcriptional lynchpin","volume":"4","author":"Devaiah","year":"2013","journal-title":"Transcription"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/nature10334","article-title":"RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia","volume":"478","author":"Zuber","year":"2011","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1038\/s41467-017-02403-5","article-title":"Brd4 binds to active enhancers to control cell identity gene induction in adipogenesis and myogenesis","volume":"8","author":"Lee","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1093\/nar\/gkw826","article-title":"BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire","volume":"45","author":"Najafova","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s12943-018-0915-9","article-title":"BRD4 and Cancer: Going beyond transcriptional regulation","volume":"17","author":"Donati","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_69","first-page":"503","article-title":"Transcription Factor Brd4, a Potential Marker of Corneal Epithelial Stem Cells","volume":"55","author":"Li","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41420-018-0066-1","article-title":"BRD4 inhibitor JQ1 inhibits and reverses mechanical injury-induced corneal scarring","volume":"4","author":"Qu","year":"2018","journal-title":"Cell Death Discov."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13045-022-01286-4","article-title":"Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer","volume":"15","author":"Zhang","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1080\/02713683.2018.1563197","article-title":"Modulation of Inflammation-Related Genes in the Cornea of a Mouse Model of Dry Eye upon Treatment with Cyclosporine Eye Drops","volume":"44","author":"Daull","year":"2019","journal-title":"Curr. Eye Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1097\/00003226-199807000-00011","article-title":"Topical modulation of interleukin-1 activity in corneal neovascularization","volume":"17","author":"Dana","year":"1998","journal-title":"Cornea"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4761","DOI":"10.1167\/iovs.08-2732","article-title":"Enhanced Experimental Corneal Neovascularization along with Aberrant Angiogenic Factor Expression in the Absence of IL-1 Receptor Antagonist","volume":"50","author":"Lu","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0014-4835(02)00293-2","article-title":"Local suppression of IL-1 by receptor antagonist in the rat model of corneal alkali injury","volume":"76","author":"Yamada","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"108017","DOI":"10.1016\/j.exer.2020.108017","article-title":"Uptake of cell debris and enhanced expression of inflammatory factors in response to dead cells in corneal fibroblast cells","volume":"194","author":"Yoon","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"199","DOI":"10.2478\/abm-2021-0026","article-title":"Wound healing of the corneal epithelium: A review","volume":"15","author":"Jalil","year":"2021","journal-title":"Asian Biomed."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Di Zazzo, A., Lee, S.M., Sung, J., Niutta, M., Coassin, M., Mashaghi, A., and Inomata, T. (2020). Variable Responses to Corneal Grafts: Insights from Immunology and Systems Biology. J. Clin. Med., 9.","DOI":"10.3390\/jcm9020586"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1182\/blood.V87.6.2095.bloodjournal8762095","article-title":"Biologic basis for interleukin-1 in disease","volume":"87","author":"Dinarello","year":"1996","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3109\/08820538.2011.588652","article-title":"Inflammatory Corneal Neovascularization: Etiopathogenesis","volume":"26","author":"Clements","year":"2011","journal-title":"Semin. Ophthalmol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1167\/iovs.61.4.7","article-title":"UV-B-Induced Inflammasome Activation Can Be Prevented by Cis-Urocanic Acid in Human Corneal Epithelial Cells","volume":"61","author":"Korhonen","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"6437","DOI":"10.1096\/fj.201902355RR","article-title":"Only IL-1 beta release is inflammasome-dependent upon ultraviolet B irradiation although IL-18 is also secreted","volume":"34","author":"Korhonen","year":"2020","journal-title":"Faseb J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"45243","DOI":"10.1074\/jbc.M207934200","article-title":"Dose-dependent biphasic activity of tRNA synthetase-associating factor, p43, in angiogenesis","volume":"277","author":"Park","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0002-9440(10)62262-6","article-title":"The novel cytokine p43 stimulates dermal fibroblast proliferation and wound repair","volume":"166","author":"Park","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_85","unstructured":"(2023, January 11). Proteomic Data. Available online: https:\/\/www.ebi.ac.uk\/pride."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/12\/2\/265\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:27:06Z","timestamp":1760120826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/12\/2\/265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,7]]},"references-count":85,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["biology12020265"],"URL":"https:\/\/doi.org\/10.3390\/biology12020265","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,7]]}}}