{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:41:42Z","timestamp":1790710902299,"version":"4.1.0"},"reference-count":91,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,16]],"date-time":"2022-10-16T00:00:00Z","timestamp":1665878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2017\/25\/N\/NZ5\/01875"],"award-info":[{"award-number":["2017\/25\/N\/NZ5\/01875"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>The search for proteomic biomarkers in ocular disease is one of the most important research directions in recent years. Reliable biomarkers can be an immense adjuvant for both diagnostic and therapeutic approaches. There is no more readily available ocular tissue for proteomic analysis than tear film, which makes an interesting target for the biomarker search. Tear film is a complex fluid consisting of a superficial lipid layer, which covers the aqueous-mucous layer. Its complexity makes it a perfect candidate for all the \u201comics\u201d approaches. Glaucoma, cataract, age-related macular degeneration, and other diseases are commonly thought to have a multifactorial background. Currently, no reliable non-invasive tests are available that would help physicians with screening and further patient management. The aim of the study is to present modern methods of measuring biomarkers in tears, with particular emphasis on spectrometric methods, and to discuss their diagnostic and therapeutic usefulness.<\/jats:p>","DOI":"10.3390\/ijerph192013341","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:04:55Z","timestamp":1665965095000},"page":"13341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Changes in Tear Proteomic Profile in Ocular Diseases"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9704-3848","authenticated-orcid":false,"given":"Mateusz","family":"Winiarczyk","sequence":"first","affiliation":[{"name":"Department of Vitreoretinal Surgery, Medical University of Lublin, 20-059 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4022-934X","authenticated-orcid":false,"given":"Katarzyna","family":"Biela","sequence":"additional","affiliation":[{"name":"Department of Vitreoretinal Surgery, Medical University of Lublin, 20-059 Lublin, Poland"},{"name":"Department of Ophthalmology, Provincial Hospital of Zamosc, 22-400 Zamosc, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Michalak","sequence":"additional","affiliation":[{"name":"Department of Epizootiology, University of Life Sciences of Lublin, 20-400 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1257-869X","authenticated-orcid":false,"given":"Dagmara","family":"Winiarczyk","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases of Small Animals, University of Life Sciences of Lublin, 20-400 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Mackiewicz","sequence":"additional","affiliation":[{"name":"Department of Vitreoretinal Surgery, Medical University of Lublin, 20-059 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,16]]},"reference":[{"key":"ref_1","first-page":"643","article-title":"Proteomic Strategies for Biomarker Identification: Progress and Challenges","volume":"2","author":"Fung","year":"2000","journal-title":"Curr. Opin. Mol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1177\/0004563217695843","article-title":"Evaluation of Commonly Used Tear Sampling Methods and Their Relevance in Subsequent Biochemical Analysis","volume":"54","author":"Rentka","year":"2017","journal-title":"Ann. Clin. Biochem."},{"key":"ref_3","first-page":"183","article-title":"Lachrymal Determinations: Methods and Updates on Biopharmaceutical and Clinical Applications","volume":"36","author":"Dumortier","year":"2004","journal-title":"ORE"},{"key":"ref_4","first-page":"529","article-title":"Concentrations of MUC16 and MUC5AC Using Three Tear Collection Methods","volume":"23","author":"Ablamowicz","year":"2017","journal-title":"Mol. Vis."},{"key":"ref_5","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."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1097\/ICO.0000000000001603","article-title":"Designing Minimally Invasive Preocular Contact Tips for Potential Application in Tear Collection","volume":"37","author":"Lee","year":"2018","journal-title":"Cornea"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1167\/tvst.9.10.23","article-title":"Quantifying Sample Collection and Processing Impacts on Fiber-Based Tear Fluid Chemical Analysis","volume":"9","author":"Barmada","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_8","first-page":"374","article-title":"The Effect of Collection Technique on Tear Composition","volume":"25","author":"Stuchell","year":"1984","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.1167\/iovs.12-11431","article-title":"Comparison of Low-Abundance Biomarker Levels in Capillary-Collected Nonstimulated Tears and Washout Tears of Aqueous-Deficient and Normal Patients","volume":"54","author":"Guyette","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3109\/02713683.2010.542867","article-title":"Validation of the Flush Method as an Alternative to Basal or Reflex Tear Collection","volume":"36","author":"Markoulli","year":"2011","journal-title":"Curr. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1097\/00003226-199707000-00013","article-title":"A Novel Method of Tear Collection: Comparison of Glass Capillary Micropipettes with Porous Polyester Rods","volume":"16","author":"Jones","year":"1997","journal-title":"Cornea"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2174\/1566524017666171101164244","article-title":"Characterization of Polyethersulfone Membranes for Tear Fluid Collection","volume":"17","author":"Yang","year":"2017","journal-title":"Curr. Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/j.1475-1313.2008.00603.x","article-title":"Tear Sample Collection Using Cellulose Acetate Absorbent Filters","volume":"28","author":"Esmaeelpour","year":"2008","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1097\/OPX.0000000000000188","article-title":"Patient Acceptability of Tear Collection in the Primary Healthcare Setting","volume":"91","author":"Quah","year":"2014","journal-title":"Optom. Vis. Sci."},{"key":"ref_15","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":"Aapola","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Jun, A.S., Cope, L., Speck, C., Feng, X., Lee, S., Meng, H., Hamad, A., and Chakravarti, S. (2011). Subnormal Cytokine Profile in the Tear Fluid of Keratoconus Patients. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016437"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1194\/jlr.M044826","article-title":"Extensive Characterization of Human Tear Fluid Collected Using Different Techniques Unravels the Presence of Novel Lipid Amphiphiles1","volume":"55","author":"Lam","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10064","DOI":"10.1038\/s41598-021-89514-8","article-title":"Diagnostic Biomarkers in Tear Fluid: From Sampling to Preanalytical Processing","volume":"11","author":"Bachhuber","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1590\/S0100-736X2013000200021","article-title":"Comparison of Two Methods of Tear Sampling for Protein Quantification by Bradford Method","volume":"33","author":"Farias","year":"2013","journal-title":"Pesq. Vet. Bras."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Jones, G., Lee, T.J., Glass, J., Rountree, G., Ulrich, L., Estes, A., Sezer, M., Zhi, W., Sharma, S., and Sharma, A. (2022). Comparison of Different Mass Spectrometry Workflows for the Proteomic Analysis of Tear Fluid. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042307"},{"key":"ref_21","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_22","first-page":"456","article-title":"Investigation of the Human Tear Film Proteome Using Multiple Proteomic Approaches","volume":"14","author":"Nichols","year":"2008","journal-title":"Mol. Vis."},{"key":"ref_23","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_24","doi-asserted-by":"crossref","unstructured":"Winiarczyk, M., Winiarczyk, D., Michalak, K., Kaarniranta, K., Adaszek, \u0141., Winiarczyk, S., and Mackiewicz, J. (2021). Dysregulated Tear Film Proteins in Macular Edema Due to the Neovascular Age-Related Macular Degeneration Are Involved in the Regulation of Protein Clearance, Inflammation, and Neovascularization. J. Clin. Med., 10.","DOI":"10.3390\/jcm10143060"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Winiarczyk, D., Winiarczyk, M., Winiarczyk, S., Michalak, K., and Adaszek, \u0141. (2020). Proteomic Analysis of Tear Film Obtained from Diabetic Dogs. Animals, 10.","DOI":"10.3390\/ani10122416"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jprot.2013.09.003","article-title":"Analysis of Protein Composition and Protein Expression in the Tear Fluid of Patients with Congenital Aniridia","volume":"94","author":"Ihnatko","year":"2013","journal-title":"J. Proteom."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1097\/OPX.0b013e3181f6fb71","article-title":"Evaluation of Extractants and Precipitants in Tear Film Proteomic Analyses","volume":"87","author":"Powell","year":"2010","journal-title":"Optom. Vis. Sci."},{"key":"ref_28","first-page":"4315","article-title":"Comparison of Protein Extraction Techniques From Tears Collected by Schirmer Strips for Proteomic Analysis","volume":"51","author":"Zhang","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","first-page":"88","article-title":"Effect of Tear Fluid Sampling and Processing on Total Protein Quantity and Electrophoretic Pattern","volume":"12","year":"2021","journal-title":"Taiwan J. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1136\/bjo.67.3.199","article-title":"Lactoferrin Levels in Normal Human Tears","volume":"67","author":"Kijlstra","year":"1983","journal-title":"Br. J. Ophthalmol."},{"key":"ref_31","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 Sj\u00f6gren Syndrome or Dry Eye Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081932"},{"key":"ref_32","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_33","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1167\/iovs.17-23358","article-title":"Age-Related Changes to Human Tear Composition","volume":"59","author":"Micera","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e9672082","DOI":"10.1155\/2016\/9672082","article-title":"Quiescent and Active Tear Protein Profiles to Predict Vernal Keratoconjunctivitis Reactivation","volume":"2016","author":"Micera","year":"2016","journal-title":"BioMed Res. Int."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sebbag, L., McDowell, E.M., Hepner, P.M., and Mochel, J.P. (2018). Effect of Tear Collection on Lacrimal Total Protein Content in Dogs and Cats: A Comparison between Schirmer Strips and Ophthalmic Sponges. BMC Vet. Res., 14.","DOI":"10.1186\/s12917-018-1390-7"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1002\/elps.1150170503","article-title":"Solubilization of Proteins for Electrophoretic Analyses","volume":"17","author":"Rabilloud","year":"1996","journal-title":"Electrophoresis"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Aluru, S.V., Agarwal, S., Srinivasan, B., Iyer, G.K., Rajappa, S.M., Tatu, U., Padmanabhan, P., Subramanian, N., and Narayanasamy, A. (2012). Lacrimal Proline Rich 4 (LPRR4) Protein in the Tear Fluid Is a Potential Biomarker of Dry Eye Syndrome. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051979"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13075-017-1228-x","article-title":"Identification of Potential Saliva and Tear Biomarkers in Primary Sj\u00f6gren\u2019s Syndrome, Utilising the Extraction of Extracellular Vesicles and Proteomics Analysis","volume":"19","author":"Aqrawi","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jtos.2017.05.008","article-title":"TFOS DEWS II Definition and Classification Report","volume":"15","author":"Craig","year":"2017","journal-title":"Ocul. Surf."},{"key":"ref_40","first-page":"71","article-title":"The Pathophysiology, Diagnosis, and Treatment of Dry Eye Disease","volume":"112","author":"Messmer","year":"2015","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1097\/NHH.0000000000000652","article-title":"Dry Eye Disease: Prevalence, Assessment, and Management","volume":"36","author":"Rouen","year":"2018","journal-title":"Home Healthc. Now"},{"key":"ref_42","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_43","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1097\/01.ico.0000133997.07144.9e","article-title":"The Lack of Association Between Signs and Symptoms in Patients With Dry Eye Disease","volume":"23","author":"Nichols","year":"2004","journal-title":"Cornea"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.preteyeres.2004.04.003","article-title":"Changes in the Tear Film and Ocular Surface from Dry Eye Syndrome","volume":"23","author":"Johnson","year":"2004","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_45","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_46","first-page":"224","article-title":"Tear Fluid Proteins in Sj\u00f6gren\u2019s Syndrome","volume":"61","author":"Janssen","year":"1986","journal-title":"Scand. J. Rheumatol. Suppl."},{"key":"ref_47","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_48","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_49","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1002\/pmic.201200230","article-title":"Proteomic Analysis Revealed the Altered Tear Protein Profile in a Rabbit Model of Sj\u00f6gren\u2019s Syndrome-Associated Dry Eye","volume":"13","author":"Zhou","year":"2013","journal-title":"Proteomics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3341\/kjo.2016.30.3.163","article-title":"Angiogenin for the Diagnosis and Grading of Dry Eye Syndrome","volume":"30","author":"Kim","year":"2016","journal-title":"Korean J. Ophthalmol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1167\/iovs.04-0448","article-title":"SELDI-TOF-MS ProteinChip Array Profiling of Tears from Patients with Dry Eye","volume":"46","author":"Grus","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Jun, J.H., Lee, Y.H., Son, M.J., and Kim, H. (2020). Importance of Tear Volume for Positivity of Tear Matrix Metalloproteinase-9 Immunoassay. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0235408"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.jtos.2020.03.006","article-title":"The Keratoconus Enigma: A Review with Emphasis on Pathogenesis","volume":"18","author":"Ferrari","year":"2020","journal-title":"Ocul. Surf."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.survophthal.2017.06.009","article-title":"A Review of Keratoconus: Diagnosis, Pathophysiology, and Genetics","volume":"62","author":"MacGregor","year":"2017","journal-title":"Surv. Ophthalmol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1097\/ICO.0000000000000408","article-title":"Global Consensus on Keratoconus and Ectatic Diseases","volume":"34","author":"Gomes","year":"2015","journal-title":"Cornea"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"101333","DOI":"10.1016\/j.clae.2020.05.002","article-title":"Diagnostic Patterns in Keratoconus","volume":"44","author":"Kreps","year":"2021","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_57","first-page":"1949","article-title":"Tear Proteomics in Keratoconus","volume":"16","author":"Pannebaker","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S1367-0484(03)00022-5","article-title":"The Cascade Hypothesis of Keratoconus","volume":"26","author":"Brown","year":"2003","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.ophtha.2004.11.050","article-title":"Inflammatory Molecules in the Tears of Patients with Keratoconus","volume":"112","author":"Lema","year":"2005","journal-title":"Ophthalmology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"76","DOI":"10.17116\/oftalma2017133576-83","article-title":"Pterygium: Etiology, pathogenesis, treatment","volume":"133","author":"Malozhen","year":"2017","journal-title":"Vestn. Oftalmol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"528","DOI":"10.5935\/0004-2749.20190103","article-title":"Mechanisms and Biomarker Candidates in Pterygium Development","volume":"82","author":"Wanzeler","year":"2019","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.preteyeres.2004.02.002","article-title":"Pathogenesis of Pterygia: Role of Cytokines, Growth Factors, and Matrix Metalloproteinases","volume":"23","author":"Chui","year":"2004","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1167\/iovs.08-2604","article-title":"Elevation of Human \u03b1-Defensins and S100 Calcium-Binding Proteins A8 and A9 in Tear Fluid of Patients with Pterygium","volume":"50","author":"Zhou","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"(2022, March 09). The Definition and Classification of Glaucoma in Prevalence Surveys|British Journal of Ophthalmology. Available online: https:\/\/bjo.bmj.com\/content\/86\/2\/238.short.","DOI":"10.1136\/bjo.86.2.238"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4225","DOI":"10.2174\/0929867325666181009153212","article-title":"Structural and Molecular Tear Film Changes in Glaucoma","volume":"26","author":"Mastropasqua","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_66","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_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.pbr.2015.05.006","article-title":"Chapter 1\u2014Molecular Biomarkers in Primary Open-Angle Glaucoma: From Noninvasive to Invasive","volume":"Volume 221","author":"Bagetta","year":"2015","journal-title":"Progress in Brain Research"},{"key":"ref_68","first-page":"e768","article-title":"Tear and Aqueous Humour Cytokine Profile in Primary Open-Angle Glaucoma","volume":"98","year":"2020","journal-title":"Acta Ophthalmol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/2211-5463.12637","article-title":"Comparative Analysis of Cytokine Profiles of Glaucomatous Tears and Aqueous Humour Reveals Potential Biomarkers for Trabeculectomy Complications","volume":"9","author":"Traverso","year":"2019","journal-title":"FEBS Open Bio"},{"key":"ref_70","first-page":"5050","article-title":"Functional Activity of Matrix Metalloproteinases 2 and 9 in Tears of Patients with Glaucoma","volume":"57","author":"Sahay","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"107837","DOI":"10.1016\/j.exer.2019.107837","article-title":"Evaluation of Tear and Aqueous Humor Level, and Genetic Variants of Connective Tissue Growth Factor as Biomarkers for Early Detection of Pseudoexfoliation Syndrome\/Glaucoma","volume":"189","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_72","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. BioSystems"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1136\/bjo.2006.101485","article-title":"Measurement of Inflammatory Cytokines by Multicytokine Assay in Tears of Patients with Glaucoma Topically Treated with Chronic Drugs","volume":"91","author":"Malvitte","year":"2007","journal-title":"Br. J. Ophthalmol."},{"key":"ref_74","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":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Reddy, S., Sahay, P., Padhy, D., Sarangi, S., Suar, M., Modak, R., and Rao, A. (2018). Tear Biomarkers in Latanoprost and Bimatoprost Treated Eyes. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201740"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.clinbiochem.2015.08.006","article-title":"Proteomic Analysis of Aqueous Humor Proteins Associated with Cataract Development","volume":"48","author":"Ji","year":"2015","journal-title":"Clin. Biochem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.3892\/mmr.2017.6345","article-title":"Identification of Proteins in the Aqueous Humor Associated with Cataract Development Using ITRAQ Methodology","volume":"15","author":"Xiang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4182","DOI":"10.1167\/iovs.10-7094","article-title":"Proteomic Analysis of Human Age-Related Nuclear Cataracts and Normal Lens Nuclei","volume":"52","author":"Su","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/prca.201400061","article-title":"Quantitative Proteomics Analysis by ITRAQ in Human Nuclear Cataracts of Different Ages and Normal Lens Nuclei","volume":"9","author":"Zhou","year":"2015","journal-title":"Proteom.-Clin. Appl."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"103881","DOI":"10.1016\/j.jprot.2020.103881","article-title":"Review of Proteomics Approach to Eye Diseases Affecting the Anterior Segment","volume":"225","author":"Aghamollaei","year":"2020","journal-title":"J. Proteom."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/prca.201200012","article-title":"Proteomic Analysis of the Aqueous Humor in Patients with Wet Age-Related Macular Degeneration","volume":"7","author":"Yao","year":"2013","journal-title":"Proteom. Clin. Appl."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.jprot.2016.06.034","article-title":"Diabetic Retinopathy: Proteomic Approaches to Help the Differential Diagnosis and to Understand the Underlying Molecular Mechanisms","volume":"150","author":"Csutak","year":"2017","journal-title":"J. Proteom."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e582060","DOI":"10.1155\/2015\/582060","article-title":"Diabetic Retinopathy: Vascular and Inflammatory Disease","volume":"2015","author":"Semeraro","year":"2015","journal-title":"J. Diabetes Res."},{"key":"ref_84","first-page":"2931","article-title":"Changes to Tear Cytokines of Type 2 Diabetic Patients with or without Retinopathy","volume":"16","author":"Liu","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Ang, W.J., Zunaina, E., Norfadzillah, A.J., Raja-Norliza, R.O., Julieana, M., Ab-Hamid, S.A., and Mahaneem, M. (2019). Evaluation of Vascular Endothelial Growth Factor Levels in Tears and Serum among Diabetic Patients. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0221481"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1039\/C9LC00975B","article-title":"Sensitive Tear Screening of Diabetic Retinopathy with Dual Biomarkers Enabled Using a Rapid Electrokinetic Patterning Platform","volume":"20","author":"Wang","year":"2020","journal-title":"Lab A Chip"},{"key":"ref_87","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_88","doi-asserted-by":"crossref","first-page":"e629529","DOI":"10.1155\/2013\/629529","article-title":"TNF-Alpha Levels in Tears: A Novel Biomarker to Assess the Degree of Diabetic Retinopathy","volume":"2013","author":"Costagliola","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1097\/OPX.0000000000001456","article-title":"Total Protein Concentration and Tumor Necrosis Factor \u03b1 in Tears of Nonproliferative Diabetic Retinopathy","volume":"96","author":"Ishak","year":"2019","journal-title":"Optom. Vis. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.ajo.2007.11.011","article-title":"Serum and Tear Levels of Nerve Growth Factor in Diabetic Retinopathy Patients","volume":"145","author":"Park","year":"2008","journal-title":"Am. J. Ophthalmol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"623619","DOI":"10.1155\/2015\/623619","article-title":"Combined Methods for Diabetic Retinopathy Screening, Using Retina Photographs and Tear Fluid Proteomics Biomarkers","volume":"2015","author":"Torok","year":"2015","journal-title":"J. Diabetes Res."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/20\/13341\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:55:05Z","timestamp":1760144105000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/20\/13341"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,16]]},"references-count":91,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijerph192013341"],"URL":"https:\/\/doi.org\/10.3390\/ijerph192013341","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,16]]}}}