{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:54:00Z","timestamp":1792590840502,"version":"4.5.0"},"reference-count":73,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,19]],"date-time":"2022-02-19T00:00:00Z","timestamp":1645228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01 EY029728"],"award-info":[{"award-number":["R01 EY029728"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30 EY031631"],"award-info":[{"award-number":["P30 EY031631"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The tear film is a multi-layer fluid that covers the corneal and conjunctival epithelia of the eye and provides lubrication, nutrients, and protection from the outside environment. Tear fluid contains a high concentration of proteins and has thus been recognized as a potential source of biomarkers for ocular disorders due to its proximity to disease sites on the ocular surface and the non-invasive nature of its collection. This is particularly true in the case of dry eye disease, which directly impacts the tear film and its components. Proteomic analysis of tear fluid is challenging mainly due to the wide dynamic range of proteins and the small sample volumes. However, recent advancements in mass spectrometry have revolutionized the field of proteomics enabling unprecedented depth, speed, and accuracy, even with small sample volumes. In this study using the Orbitrap Fusion Tribrid mass spectrometer, we compared four different mass spectrometry workflows for the proteomic analysis of tear fluid collected via Schirmer strips. We were able to establish a method of in-strip protein digestion that identified &gt;3000 proteins in human tear samples from 11 healthy subjects. Our method offers a significant improvement in the number of proteins identified compared to previously reported methods without pooling samples.<\/jats:p>","DOI":"10.3390\/ijms23042307","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T09:19:39Z","timestamp":1645435179000},"page":"2307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Comparison of Different Mass Spectrometry Workflows for the Proteomic Analysis of Tear Fluid"],"prefix":"10.3390","volume":"23","author":[{"given":"Garrett","family":"Jones","sequence":"first","affiliation":[{"name":"Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Glass","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Rountree","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lane","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Estes","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Sezer","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Zhi","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Sharma","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Ophthalmology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9597-4374","authenticated-orcid":false,"given":"Ashok","family":"Sharma","sequence":"additional","affiliation":[{"name":"Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Ophthalmology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Population Health Sciences, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1097\/ICL.0000000000000653","article-title":"The Disrupted Glycocalyx as a Source of Ocular Surface Biomarkers","volume":"46","year":"2020","journal-title":"Eye Contact Lens"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S1542-0124(12)70271-9","article-title":"A new look at lubrication of the ocular surface: Fluid mechanics behind the blinking eyelids","volume":"6","author":"Cher","year":"2008","journal-title":"Ocul. Surf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.jtos.2017.03.006","article-title":"TFOS DEWS II tear film report","volume":"15","author":"Willcox","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Lind\u00e9n, S.K., Sheng, Y.H., Every, A.L., Miles, K.M., Skoog, E.C., Florin, T.H., Sutton, P., and McGuckin, M.A. (2009). MUC1 limits Helicobacter pylori infection both by steric hindrance and by acting as a releasable decoy. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000617"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"108628","DOI":"10.1016\/j.exer.2021.108628","article-title":"Proteoglycan 4 (PRG4) expression and function in dry eye associated inflammation","volume":"208","author":"Menon","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jtos.2021.04.002","article-title":"Altered ocular surface immune cell profile in patients with dry eye disease","volume":"21","author":"Nair","year":"2021","journal-title":"Ocul. Surf."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1076\/ceyr.19.3.201.5309","article-title":"Altered cytokine balance in the tear fluid and conjunctiva of patients with Sj\u00f6gren\u2019s syndrome keratoconjunctivitis sicca","volume":"19","author":"Pflugfelder","year":"1999","journal-title":"Curr. Eye Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1586\/eop.11.56","article-title":"Post-LASIK dry eye","volume":"6","author":"Shtein","year":"2011","journal-title":"Expert Rev. Ophthalmol."},{"key":"ref_9","first-page":"1004","article-title":"Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjogren syndrome","volume":"43","author":"Balaram","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1097\/ICO.0b013e318295a2a5","article-title":"Symptoms, visual function, and mucin expression of eyes with tear film instability","volume":"32","author":"Dogru","year":"2013","journal-title":"Cornea"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.jtos.2014.02.002","article-title":"Rethinking dry eye disease: A perspective on clinical implications","volume":"12","author":"Bron","year":"2014","journal-title":"Ocul. Surf."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/aos.12012","article-title":"Correlations between commonly used objective signs and symptoms for the diagnosis of dry eye disease: Clinical implications","volume":"92","author":"Sullivan","year":"2014","journal-title":"Acta Ophthalmol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1097\/00003226-200009000-00009","article-title":"The diagnosis and management of dry eye: A twenty-five\u2013year review","volume":"19","author":"Pflugfelder","year":"2000","journal-title":"Cornea"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.17925\/EOR.2019.13.1.21","article-title":"Tear biomarkers in dry eye disease","volume":"13","author":"Chiva","year":"2019","journal-title":"Eur. Ophthalmic Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5772","DOI":"10.1038\/srep05772","article-title":"Tear proteomic analysis of Sj\u00f6gren syndrome patients with dry eye syndrome by two-dimensional-nano-liquid chromatography coupled with tandem mass spectrometry","volume":"4","author":"Li","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13363","DOI":"10.1038\/s41598-017-13817-y","article-title":"Proteomic analysis of human lacrimal and tear fluid in dry eye disease","volume":"7","author":"Jung","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ponzini, E., Santambrogio, C., De Palma, A., Mauri, P., Tavazzi, S., and Grandori, R. (2021). Mass spectrometry-based tear proteomics for noninvasive biomarker discovery. Mass Spectrom. Rev.","DOI":"10.1002\/mas.21691"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.aanat.2012.10.001","article-title":"Schirmer strip vs. capillary tube method: Non-invasive methods of obtaining proteins from tear fluid","volume":"195","author":"Posa","year":"2013","journal-title":"Ann. Anat.-Anat. Anz."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3743","DOI":"10.1038\/s41467-019-11748-y","article-title":"Orbitrap journey: Taming the ion rings","volume":"10","author":"Makarov","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3892\/ijmm.2021.4916","article-title":"Critical role of mass spectrometry proteomics in tear biomarker discovery for multifactorial ocular diseases","volume":"47","author":"Ma","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1021\/cb500904b","article-title":"Mass spectrometry-based detection and assignment of protein posttranslational modifications","volume":"10","author":"Doll","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/mas.21586","article-title":"Global and site-specific analysis of protein glycosylation in complex biological systems with Mass Spectrometry","volume":"38","author":"Xiao","year":"2019","journal-title":"Mass Spectrom. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1021\/pr800962q","article-title":"Quantitative analysis of N-linked glycoproteins in tear fluid of climatic droplet keratopathy by glycopeptide capture and iTRAQ","volume":"8","author":"Lei","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1042\/BST20170408","article-title":"Glycosylation pathways at the ocular surface","volume":"46","author":"Argueso","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Huang, Z., Du, C.X., and Pan, X.D. (2018). The use of in-strip digestion for fast proteomic analysis on tear fluid from dry eye patients. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0200702"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1021\/pr0501970","article-title":"Characterization of human tear proteome using multiple proteomic analysis techniques","volume":"4","author":"Li","year":"2005","journal-title":"J. Proteome Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"R72","DOI":"10.1186\/gb-2006-7-6-r50","article-title":"Identification of 491 proteins in the tear fluid proteome reveals a large number of proteases and protease inhibitors","volume":"7","author":"Godoy","year":"2006","journal-title":"Genome Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1016\/j.jprot.2012.04.053","article-title":"In-depth analysis of the human tear proteome","volume":"75","author":"Zhou","year":"2012","journal-title":"J. Proteom."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ab.2015.04.002","article-title":"Single unit filter-aided method for fast proteomic analysis of tear fluid","volume":"480","author":"Aass","year":"2015","journal-title":"Anal. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.exer.2018.10.006","article-title":"Investigation of the global protein content from healthy human tears","volume":"179","author":"Dor","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s00417-018-3984-y","article-title":"Tear film proteome in age-related macular degeneration","volume":"256","author":"Winiarczyk","year":"2018","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jtos.2016.09.005","article-title":"Tear Fluid Protein Changes in Dry Eye Syndrome Associated with Rheumatoid Arthritis: A Proteomic Approach","volume":"15","author":"Aluru","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1038\/eye.2010.7","article-title":"Tear proteomics in evaporative dry eye disease","volume":"24","author":"Versura","year":"2010","journal-title":"Eye"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4889","DOI":"10.1021\/pr900686s","article-title":"Identification of tear fluid biomarkers in dry eye syndrome using iTRAQ quantitative proteomics","volume":"8","author":"Zhou","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.jprot.2012.11.017","article-title":"Tear proteome and protein network analyses reveal a novel pentamarker panel for tear film characterization in dry eye and meibomian gland dysfunction","volume":"78","author":"Soria","year":"2013","journal-title":"J. Proteom."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1016\/j.jprot.2012.01.019","article-title":"Quantitative analysis of proteins in the tear fluid of patients with diabetic retinopathy","volume":"75","author":"Csosz","year":"2012","journal-title":"J. Proteom."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kuo, M.T., Fang, P.C., Chao, T.L., Chen, A., Lai, Y.H., Huang, Y.T., and Tseng, C.Y. (2019). Tear Proteomics Approach to Monitoring Sjogren Syndrome or Dry Eye Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081932"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.clinbiochem.2011.10.006","article-title":"Comparison of tear proteins between healthy and early diabetic retinopathy patients","volume":"45","author":"Kim","year":"2012","journal-title":"Clin. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1039\/C1MB05357D","article-title":"Differential protein expression in tears of patients with primary open angle and pseudoexfoliative glaucoma","volume":"8","author":"Pieragostino","year":"2012","journal-title":"Mol. Biosyst."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1039\/c3mb25463a","article-title":"Shotgun proteomics reveals specific modulated protein patterns in tears of patients with primary open angle glaucoma naive to therapy","volume":"9","author":"Pieragostino","year":"2013","journal-title":"Mol. Biosyst."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"12038","DOI":"10.1038\/s41598-018-30369-x","article-title":"Patient stratification in clinical glaucoma trials using the individual tear proteome","volume":"8","author":"Nattinen","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1038\/eye.2011.105","article-title":"Changes in tear protein profile in keratoconus disease","volume":"25","author":"Acera","year":"2011","journal-title":"Eye"},{"key":"ref_43","first-page":"1949","article-title":"Tear proteomics in keratoconus","volume":"16","author":"Pannebaker","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1007\/s10792-017-0672-6","article-title":"Comparative proteome analysis of the tear samples in patients with low-grade keratoconus","volume":"38","author":"Yenihayat","year":"2018","journal-title":"Int. Ophthalmol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jprot.2017.09.001","article-title":"Thyroid-associated orbitopathy and tears: A proteomics study","volume":"170","author":"Kishazi","year":"2018","journal-title":"J. Proteom."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3892\/etm.2020.9383","article-title":"Tear proteomics of orbital decompression for disfiguring exophthalmos in inactive thyroid-associated ophthalmopathy","volume":"20","author":"Jiang","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.2147\/OPTH.S95242","article-title":"Tear film osmolarity and dry eye disease: A review of the literature","volume":"9","author":"Potvin","year":"2015","journal-title":"Clin. Ophthalmol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9426","DOI":"10.1038\/s41598-020-66442-7","article-title":"Characterization of Tear Immunoglobulins in a Small-Cohort of Keratoconus Patients","volume":"10","author":"McKay","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_49","first-page":"623","article-title":"Origin and biosynthesis of human tear fluid proteins","volume":"24","author":"Janssen","year":"1983","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.1016\/j.molimm.2007.06.145","article-title":"The role of complement system in ocular diseases including uveitis and macular degeneration","volume":"44","author":"Jha","year":"2007","journal-title":"Mol. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.tem.2010.10.001","article-title":"High density lipoprotein: It\u2019s not just about lipid transport anymore","volume":"22","author":"Gordon","year":"2011","journal-title":"Trends Endocrinol. Metab. TEM"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/ajcn\/nqy136","article-title":"Rethinking apolipoprotein A-II in lipid metabolism","volume":"108","author":"Pownall","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1097\/ICL.0b013e318184bdb6","article-title":"Topical apolipoprotein A-1 may have a beneficial effect on the corneal epithelium in a mouse model of dry eye: A pilot study","volume":"34","author":"Nyunt","year":"2008","journal-title":"Eye Contact Lens"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1167\/iovs.13-12080","article-title":"Tear proteomic analysis of patients with type 2 diabetes and dry eye syndrome by two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry","volume":"55","author":"Li","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1167\/iovs.12-11084","article-title":"Effects of Keratin and Lung Surfactant Proteins on the Surface Activity of Meibomian Lipids","volume":"54","author":"Palaniappan","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Jester, J.V., Parfitt, G.J., and Brown, D.J. (2015). Meibomian gland dysfunction: Hyperkeratinization or atrophy?. BMC Ophthalmol., 15.","DOI":"10.1186\/s12886-015-0132-x"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0167-4889(00)00005-7","article-title":"Myosins: A diverse superfamily","volume":"1496","author":"Sellers","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1471-4159.2010.07110.x","article-title":"The role of myosin V in exocytosis and synaptic plasticity","volume":"116","author":"Rudolf","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.mcn.2017.05.006","article-title":"Membrane shaping by actin and myosin during regulated exocytosis","volume":"84","author":"Papadopulos","year":"2017","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7223","DOI":"10.1167\/iovs.13-12887","article-title":"Myosin 6 is required for iris development and normal function of the outer retina","volume":"54","author":"Samuels","year":"2013","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"29629","DOI":"10.1038\/srep29629","article-title":"Proteomics analysis of human tears from aqueous-deficient and evaporative dry eye patients","volume":"6","author":"Perumal","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_62","first-page":"604","article-title":"The role of lactoferrin in the iron metabolism. Part II. Antimicrobial and antiinflammatory effect of lactoferrin by chelation of iron","volume":"64","author":"Artym","year":"2010","journal-title":"Postepy Hig. Med. Dosw. Online"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Vagge, A., Senni, C., Bernabei, F., Pellegrini, M., Scorcia, V., Traverso, C.E., and Giannaccare, G. (2020). Therapeutic Effects of Lactoferrin in Ocular Diseases: From Dry Eye Disease to Infections. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186668"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1097\/OPX.0000000000000888","article-title":"Contact Lens-Induced Discomfort and Protein Changes in Tears","volume":"93","author":"Masoudi","year":"2016","journal-title":"Optom. Vis. Sci. Off. Publ. Am. Acad. Optom."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.exer.2010.08.018","article-title":"Focus on Molecules: Tear lipocalin","volume":"92","author":"Glasgow","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1007\/s10067-020-05033-3","article-title":"Serum 14-3-3\u03b7 protein is associated with clinical and serologic features of Sj\u00f6gren\u2019s syndrome in patients with systemic lupus erythematosus: A cross-sectional analysis","volume":"39","author":"Hammam","year":"2020","journal-title":"Clin. Rheumatol."},{"key":"ref_67","first-page":"563","article-title":"Acute-phase proteins in inflammation","volume":"189","author":"Engler","year":"1995","journal-title":"Comptes Rendus Seances Soc. Biol. Ses Fil."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12348-020-00204-4","article-title":"Unilateral acute anterior uveitis is associated with ipsilateral changes in the tear fluid proteome that involves the LXR\/RXR pathway","volume":"10","author":"Eidet","year":"2020","journal-title":"J. Ophthalmic Inflamm. Infect."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1167\/tvst.9.3.16","article-title":"Comparison of Capillary and Schirmer Strip Tear Fluid Sampling Methods Using SWATH-MS Proteomics Approach","volume":"9","author":"Nattinen","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_70","unstructured":"Tukey, J.W. (1977). Exploratory Data Analysis, Addison-Wesley."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13167-016-0065-3","article-title":"Tear fluid biomarkers in ocular and systemic disease: Potential use for predictive, preventive and personalised medicine","volume":"7","author":"Hagan","year":"2016","journal-title":"EPMA J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s12014-020-09307-5","article-title":"Tear proteomic profile in three distinct ocular surface diseases: Keratoconus, pterygium, and dry eye related to graft-versus-host disease","volume":"17","author":"Alborghetti","year":"2020","journal-title":"Clin. Proteom."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"7385","DOI":"10.1167\/iovs.10-6532","article-title":"Proteomic profiling of inflammatory signaling molecules in the tears of patients on chronic glaucoma medication","volume":"52","author":"Wong","year":"2011","journal-title":"Invest. Ophthalmol. Vis. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/4\/2307\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:23:03Z","timestamp":1760134983000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/4\/2307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,19]]},"references-count":73,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23042307"],"URL":"https:\/\/doi.org\/10.3390\/ijms23042307","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,19]]}}}