{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:40:28Z","timestamp":1747183228105,"version":"3.40.5"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T00:00:00Z","timestamp":1697241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>The management of blepharitis continues to challenge clinicians due to the poorly understood aetiology of the condition. We recently identified the family of intracellular plakin proteins as essential driving forces underlying anterior blepharitis. A large\u2010scale protein analysis was used to study if a topical dexamethasone\/tobramycin solution could be used to reverse the expression of plakin proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Tear film samples from treatment na\u00efve patients with anterior blepharitis (<jats:italic>n<\/jats:italic>\u2009=\u200915) were collected with Schirmer filtration paper. A subgroup of the patients (<jats:italic>n<\/jats:italic>\u2009=\u200910) received treatment with a dexamethasone\/tobramycin 1\u2009+\u20093\u2009mg\/mL ophthalmic suspension (Tobradex<jats:sup>\u00ae<\/jats:sup>) for 3\u2009weeks and collection of tear film samples was repeated. The samples were analysed with label\u2010free quantification nano liquid chromatography\u2013tandem mass spectrometry requiring quantification in at least 70% of the samples in each group. Proteins were considered differentially expressed if <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Following Tobradex<jats:sup>\u00ae<\/jats:sup> intervention, 27 proteins were upregulated while 61 proteins were downregulated. Regulated proteins after Tobradex<jats:sup>\u00ae<\/jats:sup> treatment were involved in intermediate filament cytoskeleton organization including downregulation of the plakin proteins envoplakin, epiplakin and periplakin. Plectin, a protein of the plakin family, remained unchanged after Tobradex<jats:sup>\u00ae<\/jats:sup> therapy. Tobradex<jats:sup>\u00ae<\/jats:sup> treatment resulted in the regulation of proteins involved in translation including a cluster of downregulated ribosomal proteins. Tobradex<jats:sup>\u00ae<\/jats:sup> intervention was associated with the regulation of proteins involved in fructose metabolism and glycolytic processes including fructose\u20101.6\u2010bisphosphatase 1, fructose\u2010bisphosphate aldolases A and B, pyruvate kinase PKM and transketolase. Ig lambda chain V\u2010I region, prominin\u20101, and protein Niban were upregulated after Tobradex<jats:sup>\u00ae<\/jats:sup> treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Tobradex treatment reversed the expression of plakin proteins in anterior blepharitis. Topical solutions which inhibit the expression of plakin proteins may have the potential to restore the ocular surface integrity in anterior blepharitis and should be explored further.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aos.15792","type":"journal-article","created":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T09:41:16Z","timestamp":1697276476000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tear film proteome changes following Tobradex<sup>\u00ae<\/sup> therapy in anterior blepharitis"],"prefix":"10.1111","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4304-9704","authenticated-orcid":false,"given":"Danson Vasanthan","family":"Muttuvelu","sequence":"first","affiliation":[{"name":"Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2150-7754","authenticated-orcid":false,"given":"Lasse J\u00f8rgensen","family":"Cehofski","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Odense University Hospital  Odense Denmark"},{"name":"Department of Clinical Research University of Southern Denmark  Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tor Paaske","family":"Utheim","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry Oslo University Hospital  Oslo Norway"},{"name":"The Norwegian Dry Eye Clinic  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0331-9028","authenticated-orcid":false,"given":"Xiangjun","family":"Chen","sequence":"additional","affiliation":[{"name":"The Norwegian Dry Eye Clinic  Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Vorum","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Aalborg University Hospital  Aalborg Denmark"},{"name":"Department of Clinical Medicine Aalborg University  Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie Louise Roed","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Rigshospitalet University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5906-7670","authenticated-orcid":false,"given":"Steffen","family":"Heegaard","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Rigshospitalet University of Copenhagen  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asif Manzoor","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed Basim","family":"Abduljabar","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bent","family":"Honor\u00e9","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aalborg University  Aalborg Denmark"},{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2018.10.019"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-017-1228-x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mie.2015.06.019"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.498"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-200310000-00008"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25487"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18050907"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.64.2.23"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.14.6"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113328"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.06.011"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27175687"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2018.02.029"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.14.227"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2022.2047206"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2019.107722"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1120672119854985"},{"key":"e_1_2_6_19_1","article-title":"Functional enrichment analysis of regulatory elements","volume":"10","author":"Garcia\u2010Moreno A.","year":"2022","journal-title":"Biomedicine"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S407805"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.15.151"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0255-3_3"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S110739"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202733"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073714"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00396"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-11077"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-0124(12)70620-1"},{"key":"e_1_2_6_29_1","article-title":"Interventions for chronic blepharitis","volume":"2012","author":"Lindsley K.","year":"2012","journal-title":"The Cochrane Database of Systematic Reviews"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-02137-4"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2023.01.009"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(93)31643-X"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2020.118801"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2023.06.010"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.9.3.16"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2006.097352"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.118.5.615"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1003"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1131"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw937"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2006.0084"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007995.2010.539603"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.136"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-18467"}],"container-title":["Acta Ophthalmologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aos.15792","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T03:26:38Z","timestamp":1718076398000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aos.15792"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,14]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1111\/aos.15792"],"URL":"https:\/\/doi.org\/10.1111\/aos.15792","archive":["Portico"],"relation":{},"ISSN":["1755-375X","1755-3768"],"issn-type":[{"type":"print","value":"1755-375X"},{"type":"electronic","value":"1755-3768"}],"subject":[],"published":{"date-parts":[[2023,10,14]]},"assertion":[{"value":"2023-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}