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Review

Bio-chemical markers of chronic, non-infectious disease in the human tear film

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Pages 166-176 | Received 12 Mar 2021, Accepted 25 Aug 2021, Published online: 30 Sep 2021

References

  • Willcox MDP, Argueso P, Georgiev GA, et al. TFOS DEWS II tear film report. Ocul Surf. 2017;15:366–403.
  • Postnikoff CK, Held K, Viswanath V, et al. Enhanced closed eye neutrophil degranulation in dry eye disease. Ocul Surf. 2020;18:841–851.
  • Kenny A, Jiménez-Mateos EM, Zea-Sevilla MA, et al. Proteins and microRNAs are differentially expressed in tear fluid from patients with Alzheimer’s disease. Sci Rep. 2019;9:15437.
  • Markoulli M, Papas E, Petznick A, et al. Validation of the flush method as an alternative to basal or reflex tear collection. Curr Eye Res. 2011;36:198–207.
  • Markoulli M, Gokhale M, You J. Substance P in flush tears and schirmer strips of healthy participants. Optometry Vision Sci. 2017;94:527–533.
  • Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95.
  • Amur S. Biomarker technology: speaking the same language. cited 2021 Jul 8th. Available from: https://www.fda.gov/media/102547/download
  • Green-Church KB, Nichols KK, Kleinholz NM, et al. Investigation of the human tear film proteome using multiple proteomic approaches. Mol Vis. 2008;14:456–470.
  • Markoulli M, Papas E, Cole N, et al. The diurnal variation of matrix metalloproteinase-9 and its associated factors in human tears. Invest Ophthalmol Vis Sci. 2012;53:1479–1484.
  • Markoulli M, Papas E, Cole N, et al. Effect of contact lens wear on the diurnal profile of matrix metalloproteinase 9 in tears. Optom Vis Sci. 2013;90:419–429.
  • Sapra A BP. Diabetes Mellitus. 2020
  • Duby JJ, Campbell RK, Setter SM, et al. Diabetic neuropathy: an intensive review. Am J Health Syst Pharm. 2004;61:160-173; quiz 175-166.
  • Ting DS, Cheung GC, Wong TY. Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review. Clin Exp Ophthalmol. 2016;44:260–277.
  • Furuichi K, Shimizu M, Okada H, et al. Clinico-pathological features of kidney disease in diabetic cases. Clin Exp Nephrol. 2018;22:1046–1051.
  • Zhao Z, Liu J, Shi B, et al. Advanced glycation end product (AGE) modified proteins in tears of diabetic patients. Mol Vis. 2010;16:1576–1584.
  • Csősz É, Boross P, Csutak A, et al. Quantitative analysis of proteins in the tear fluid of patients with diabetic retinopathy. J Proteomics. 2012;75:2196–2204.
  • Torok Z, Peto T, Csosz E, et al. Tear fluid proteomics multimarkers for diabetic retinopathy screening. BMC Ophthalmol. 2013;13:40.
  • Li B, Sheng M, Xie L, et al. Tear proteomic analysis of patients with type 2 diabetes and dry eye syndrome by two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry. Invest Ophthalmol Vis Sci. 2014;55:177–186.
  • Pinazo-Durán MD, Zanón-Moreno V, Lleó-Perez A, et al. Genetic systems for a new approach to risk of progression of diabetic retinopathy. Arch Soc Esp Oftalmol. 2016;91:209–216.
  • Markoulli M, You J, Kim J, et al. Corneal nerve morphology and tear film substance P in diabetes. Optometry Vision Sci. 2017;94:726–731.
  • Stuard WL, Titone R, Robertson DM. Tear levels of insulin-like growth factor binding protein 3 correlate with subbasal nerve plexus changes in patients with type 2 diabetes mellitus. Invest Ophthalmol Vis Sci. 2017;58:6105–6112.
  • Liu R, Ma B, Gao Y, et al. Tear inflammatory cytokines analysis and clinical correlations in diabetes and nondiabetes with dry eye. Am J Ophthalmol. 2019;200:10–15.
  • Tummanapalli SS, Willcox MDP, Issar T, et al. Tear film substance P: a potential biomarker for diabetic peripheral neuropathy. Ocul Surf. 2019;17:690–698.
  • Iyengar MF, Soto LF, Requena D, et al. Tear biomarkers and corneal sensitivity as an indicator of neuropathy in type 2 diabetes. Diabetes Res Clin Pract. 2020;163:108143.
  • Stuard WL, Titone R, Robertson DM. Tear levels of IGFBP-3: a potential biomarker for diabetic nerve changes in the cornea. Eye Contact Lens. 2020; 46:319–325.
  • Grus FH, Sabuncuo P, Dick HB, et al. Changes in the tear proteins of diabetic patients. BMC Ophthalmol. 2002;2:4.
  • Lane JD, Krumholz DM, Sack RA, et al. Tear glucose dynamics in diabetes mellitus. Curr Eye Res. 2006;31:895–901.
  • Yu L, Chen X, Qin G, et al. Tear film function in type 2 diabetic patients with retinopathy. Ophthalmol J Int D’ophtalmologie Int J Ophthalmol Zeitschrift Fur Augenheilkunde. 2008;222:284–291.
  • Liu J, Shi B, He S, et al. Changes to tear cytokines of type 2 diabetic patients with or without retinopathy. Mol Vis. 2010;16:2931–2938.
  • Yang Q, Li B, Sheng M. Meibum lipid composition in type 2 diabetics with dry eye. Exp Eye Res. 2021;206:108522.
  • Lewis JG, Stephens PJ. Tear glucose in diabetics. Br J Ophthalmol. 1958;42:754–758.
  • Sen DK, Sarin GS. Tear glucose levels in normal people and in diabetic patients. Br J Ophthalmol. 1980;64:693–695.
  • Van Haeringen NJ, Glasius E. Collection method dependent concentrations of some metabolites in human tear fluid, with special reference to glucose in hyperglycaemic conditions. Albrecht von Graefes Archiv für Klinische und Experimentelle Ophthalmologie. 1977;202:1–7.
  • Aihara M, Kubota N, Minami T, et al. Association between tear and blood glucose concentrations: random intercept model adjusted with confounders in tear samples negative for occult blood. J Diabetes Investig. 2020; 12:266–276.
  • Baca JT, Finegold DN, Asher SA. Tear glucose analysis for the noninvasive detection and monitoring of diabetes mellitus. Ocul Surf. 2007;5:280–293.
  • Liao Y, Yao H, Lingley A, et al. A 3 microW CMOS glucose sensor for wireless contact-lens tear glucose monitoring. IEEE J Solid-State Circuits. 2012;47:335–344.
  • Otis B. Update on our smart lens program with alcon. 2018 Nov cited 2021 Jul 8th. Available from: https://blog.verily.com/2018/11/update-on-our-smart-lens-program-with.html
  • Kim HJ, Kim PK, Yoo HS, et al. Comparison of tear proteins between healthy and early diabetic retinopathy patients. Clin Biochem. 2012;45:60–67.
  • Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–297.
  • Kunnen CM, Brown SH, Lazon de la Jara P, et al. Influence of meibomian gland expression methods on human lipid analysis results. Ocul Surf. 2016;14:49–55.
  • Brown SH, Kunnen CM, Duchoslav E, et al. A comparison of patient matched meibum and tear lipidomes. Invest Ophthalmol Vis Sci. 2013;54:7417–7424.
  • Khan AR, Awan FR. Metals in the pathogenesis of type 2 diabetes. J Diabetes Metab Disord. 2014;13:16.
  • Cancarini A, Fostinelli J, Napoli L, et al. Trace elements and diabetes: assessment of levels in tears and serum. Exp Eye Res. 2017;154:47–52.
  • Pritchard N, Edwards K, Russell AW, et al. Corneal confocal microscopy predicts 4-year incident peripheral neuropathy in type 1 diabetes. Diabetes Care. 2015;38:671–675.
  • Moschos MM, Rouvas AA, Papadimitriou S, et al. Quantitative determination of glycosaminoglycans in tears of diabetic patients. Clin Ophthalmol. 2008;2:581–584.
  • Sodhi H, Panitch A. Glycosaminoglycans in tissue engineering: a review. Biomolecules. 2021;11:1–22.
  • Lepedda AJ, De Muro P, Capobianco G, et al. Significance of urinary glycosaminoglycans/proteoglycans in the evaluation of type 1 and type 2 diabetes complications. J Diabetes Complications. 2017;31:149–155.
  • Costagliola C, Romano V, De Tollis M, et al. TNF-alpha levels in tears: a novel biomarker to assess the degree of diabetic retinopathy. Mediators Inflamm. 2013;2013:629529.
  • Joussen AM, Doehmen S, Le ML, et al. TNF-alpha mediated apoptosis plays an important role in the development of early diabetic retinopathy and long-term histopathological alterations. Mol Vis. 2009;15:1418–1428.
  • Wei Y, Gadaria-Rathod N, Epstein S, et al. Tear cytokine profile as a noninvasive biomarker of inflammation for ocular surface diseases: standard operating procedures. Invest Ophthalmol Vis Sci. 2013;54:8327–8336.
  • Ang WJ, Zunaina E, Norfadzillah AJ, et al. Evaluation of vascular endothelial growth factor levels in tears and serum among diabetic patients. Plos One. 2019;14:e0221481–e0221481.
  • Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994;331:1480–1487.
  • Kawai S, Nakajima T, Hokari S, et al. Apolipoprotein A-I concentration in tears in diabetic retinopathy. Ann Clin Biochem. 2002;39:56–61.
  • Gessl A, Lemmens-Gruber R, Kautzky-Willer A. Thyroid disorders. In: Regitz-Zagrosek V, editor. Sex and gender differences in pharmacology. Berlin, Heidelberg: Springer Berlin Heidelberg; 2012. p. 361–386.
  • De Leo S, Lee SY, Braverman LE. Hyperthyroidism. Lancet. 2016;388:906–918.
  • Chaker L, Bianco AC, Jonklaas J, et al. Hypothyroidism. Lancet. 2017;390:1550–1562.
  • Xu N, Cui Y, Fu D, et al. Tear inflammatory cytokines and ocular surface changes in patients with active thyroid eye disease treated with high-dose intravenous glucocorticoids. J Endocrinol Invest. 2020;43:901–910.
  • Song RH, Wang B, Yao QM, et al. Proteomics screening of differentially expressed cytokines in tears of patients with Graves’ ophthalmopathy. Endocr Metab Immune Disord Drug Targets. 2020;20:87–95.
  • Chen Q. The expression of interleukin-15 and interleukin-17 in tears and orbital tissues of Graves ophthalmopathy patients. J Cell Biochem. 2019;120:6299–6303.
  • Yang M, Chung Y, Lang S, et al. The tear cytokine profile in patients with active Graves’ orbitopathy. Endocrine. 2018;59:402–409.
  • Mandić JJ, Kozmar A, Kusačić-Kuna S, et al. The levels of 12 cytokines and growth factors in tears: hyperthyreosis vs euthyreosis. Graefe’s Arch Clin Exp Ophthalmol. 2018;256:845–852.
  • Kishazi E, Dor M, Eperon S, et al. Differential profiling of lacrimal cytokines in patients suffering from thyroid-associated orbitopathy. Sci Rep. 2018;8:10792.
  • Kishazi E, Dor M, Eperon S, et al. Thyroid-associated orbitopathy and tears: a proteomics study. J Proteomics. 2018;170:110–116.
  • Choi W, Li Y, Ji YS, et al. Oxidative stress markers in tears of patients with Graves’ orbitopathy and their correlation with clinical activity score. BMC Ophthalmol. 2018;18:303.
  • Aass C, Norheim I, Eriksen EF, et al. Establishment of a tear protein biomarker panel differentiating between Graves’ disease with or without orbitopathy. Plos One. 2017;12:e0175274.
  • Aass C, Norheim I, Eriksen EF, et al. Comparative proteomic analysis of tear fluid in Graves’ disease with and without orbitopathy. Clin Endocrinol (Oxf). 2016;85:805–812.
  • Jiang L, Mou P, Wei R. [Expressions of lysozyme C and lactoferrin in tears of thyroid-associated ophthalmopathy patients]. Zhonghua Yi Xue Za Zhi. 2015;95:749–752.
  • Huang D, Luo Q, Yang H, et al. Changes of lacrimal gland and tear inflammatory cytokines in thyroid-associated ophthalmopathy. Invest Ophthalmol Vis Sci. 2014;55:4935–4943.
  • Cai K, Wei R. Interleukin-7 expression in tears and orbital tissues of patients with Graves’ ophthalmopathy. Endocrine. 2013;44:140–144.
  • Ujhelyi B, Gogolak P, Erdei A, et al. Graves’ orbitopathy results in profound changes in tear composition: a study of plasminogen activator inhibitor-1 and seven cytokines. Thyroid. 2012;22:407–414.
  • Matheis N, Okrojek R, Grus FH, et al. Proteomics of tear fluid in thyroid-associated orbitopathy. Thyroid. 2012;22:1039–1045.
  • Huang D, Xu N, Song Y, et al. Inflammatory cytokine profiles in the tears of thyroid-associated ophthalmopathy. Graefe’s Arch Clin Exp Ophthalmol. 2012;250:619–625.
  • Yoon JS, Choi SH, Lee JH, et al. Ocular surface inflammation, and nerve growth factor level in tears in active thyroid-associated ophthalmopathy. Graefe’s Arch Clin Exp Ophthalmol. 2010;248:271–276.
  • Baker GR, Morton M, Rajapaska RS, et al. Altered tear composition in smokers and patients with graves ophthalmopathy. Arch Ophthalmol (Chicago, Ill : 1960). 2006;124:1451–1456.
  • Khalil HA, De Keizer RJ, Bodelier VM, et al. Secretory IgA and lysozyme in tears of patients with Graves’ ophthalmopathy. Documenta Ophthalmologica Adv Ophthalmol. 1989;72:329–334.
  • Khalil HA, de Keizer RJ, Kijlstra A. Analysis of tear proteins in Graves’ ophthalmopathy by high performance liquid chromatography. Am J Ophthalmol. 1988;106:186–190.
  • Mourits MP, Prummel MF, Wiersinga WM, et al. Clinical activity score as a guide in the management of patients with Graves’ ophthalmopathy. Clin Endocrinol (Oxf). 1997;47:9–14.
  • Oh J, Vidal-Jordana A, Montalban X. Multiple sclerosis: clinical aspects. Curr Opin Neurol. 2018;31:752–759.
  • Miller DH, Chard DT, Ciccarelli O. Clinically isolated syndromes. Lancet Neurol. 2012;11:157–169.
  • Link H, Huang Y-M. Oligoclonal bands in multiple sclerosis cerebrospinal fluid: an update on methodology and clinical usefulness. J Neuroimmunol. 2006;180:17–28.
  • Coyle PK, Sibony PA. Tear analysis in multiple sclerosis. Neurology. 1986;36:547–550.
  • Devos D, Forzy G, de Seze J, et al. Silver stained isoelectrophoresis of tears and cerebrospinal fluid in multiple sclerosis. J Neurol. 2001;248:672–675.
  • Calais G, Forzy G, Crinquette C, et al. Tear analysis in clinically isolated syndrome as new multiple sclerosis criterion. Mult Scler. 2010;16:87–92.
  • Hümmert MW, Wurster U, Bönig L, et al. Investigation of oligoclonal IgG bands in tear fluid of multiple sclerosis patients. Front Immunol. 2019;10:1110.
  • Martino G, Servalli C, Filippi M, et al. Absence of oligoclonally restricted immunoglobulins in tears from multiple sclerosis patients. J Neuroimmunol. 1993;44:149–155.
  • Liedtke W, Weller M, Wiethölter H, et al. Immunological abnormalities in the tears of multiple sclerosis patients. Acta Neurol Scand. 1992;85:228–230.
  • Cicalini I, Rossi C, Pieragostino D, et al. Integrated lipidomics and metabolomics analysis of tears in multiple sclerosis: an insight into diagnostic potential of lacrimal fluid. Int J Mol Sci. 2019;20:1265.
  • Salvisberg C, Tajouri N, Hainard A, et al. Exploring the human tear fluid: discovery of new biomarkers in multiple sclerosis. Proteomics Clin Appl. 2014;8:185–194.
  • Hamm-Alvarez SF, Janga SR, Edman MC, et al. Levels of oligomeric α-synuclein in reflex tears distinguish Parkinson’s disease patients from healthy controls. Biomark Med. 2019;13:1447–1457.
  • Spillantini MG, Schmidt ML, Lee VMY, et al. α-synuclein in Lewy bodies. Nature. 1997;388:839–840.
  • Stefanis L. α-Synuclein in Parkinson’s disease. Cold Spring Harb Perspect Med. 2012;2:a009399–a009399.
  • Hamm-Alvarez SF, Okamoto CT, Janga SR, et al. Oligomeric α-synuclein is increased in basal tears of Parkinson’s patients. Biomark Med. 2019;13:941–952.
  • Maass F, Rikker S, Dambeck V, et al. Increased alpha-synuclein tear fluid levels in patients with Parkinson’s disease. Sci Rep. 2020;10:8507.
  • Çomoğlu SS, Güven H, Acar M, et al. Tear levels of tumor necrosis factor-alpha in patients with Parkinson’s disease. Neurosci Lett. 2013;553:63–67.
  • Boerger M, Funke S, Leha A, et al. Proteomic analysis of tear fluid reveals disease-specific patterns in patients with Parkinson’s disease - A pilot study. Parkinsonism Relat Disord. 2019;63:3–9.
  • WHO. Dementia. cited 2021 Jul 8. Available from: https://www.who.int/news-room/fact-sheets/detail/dementia
  • Cennamo G, Montorio D, Morra VB, et al. Surface-enhanced Raman spectroscopy of tears: toward a diagnostic tool for neurodegenerative disease identification. J Biomed Opt. 2020;25:1–12.
  • Shigemoto Y, Sone D, Maikusa N et al. Association of deposition of tau and amyloid-β proteins with structural connectivity changes in cognitively normal older adults and Alzheimer’s disease spectrum patients. Brain Behav. Elsevier; 2018;8:e01145.
  • Mondragón-Rodríguez S, Perry G, Peña-Ortega F. Chapter 8 - Tau proteins. In: Adejare A, editor. Drug discovery approaches for the treatment of neurodegenerative disorders. Academic Press; 2017. p. 145–160.
  • O’Brien RJ, Wong PC. Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci. 2011;34:185–204.
  • Twohig D, Nielsen HM. α-synuclein in the pathophysiology of Alzheimer’s disease. Mol Neurodegener. 2019;14:23.
  • Kalló G, Emri M, Varga Z, et al. Changes in the chemical barrier composition of tears in Alzheimer’s disease reveal potential tear diagnostic biomarkers. Plos One. 2016;11:e0158000.
  • Khusro A, Aarti C, Barbabosa-Pliego A, et al. Neoteric advancement in TB drugs and an overview on the anti-tubercular role of peptides through computational approaches. Microb Pathog. 2018;114:80–89.
  • Buse DC, Greisman JD, Baigi K, et al. Migraine progression: a systematic review. Headache. 2019;59:306–338.
  • Villalón CM, Olesen J. The role of CGRP in the pathophysiology of migraine and efficacy of CGRP receptor antagonists as acute antimigraine drugs. Pharmacol Ther. 2009;124:309–323.
  • Kamm K, Straube A, Ruscheweyh R. Calcitonin gene-related peptide levels in tear fluid are elevated in migraine patients compared to healthy controls. Cephalalgia. 2019;39:1535–1543.
  • Mohanty D, Lippmann S. CGRP inhibitors for migraine. Innov Clin Neurosci. 2020;17:39–40.
  • Rentka A, Harsfalvi J, Szucs G, et al. Membrane array and multiplex bead analysis of tear cytokines in systemic sclerosis. Immunol Res. 2016;64:619–626.
  • Naehrig S, Chao C-M, Naehrlich L. Cystic fibrosis. Dtsch Arztebl Int. 2017;114:564–574.
  • Mrugacz M, Kaczmarski M, Bakunowicz-Lazarczyk A, et al. IL-8 and IFN-γ in tear fluid of patients with cystic fibrosis. J Interferon Cytokine Res. 2006;26:71–75.
  • Mrugacz M, Zelazowska B, Bakunowicz-Lazarczyk A, et al. Elevated tear fluid levels of MIP-1alpha in patients with cystic fibrosis. J Interferon Cytokine Res. 2007;27:491–495.
  • Bhavsar I, Miller CS, Al-Sabbagh M. Macrophage inflammatory protein-1 alpha (MIP-1 alpha)/CCL3: as a biomarker. In: Preedy VR, Patel VB, editors. General methods in biomarker research and their applications. Dordrecht: Springer Netherlands; 2015. p. 223–249.
  • Brücher BL, Jamall IS. Epistemology of the origin of cancer: a new paradigm. BMC Cancer. 2014;14:331.
  • Ding D, Han S, Zhang H, et al. Predictive biomarkers of colorectal cancer. Comput Biol Chem. 2019;83:107106.
  • Fabris L, Ceder Y, Chinnaiyan AM, et al. The potential of microRNAs as prostate cancer biomarkers. Eur Urol. 2016;70:312–322.
  • Adhami M, Haghdoost AA, Sadeghi B, et al. Candidate miRNAs in human breast cancer biomarkers: a systematic review. Breast Cancer. 2018;25:198–205.
  • Das V, Kalita J, Pal M. Predictive and prognostic biomarkers in colorectal cancer: a systematic review of recent advances and challenges. Biomed Pharmacothe. 2017;87:8–19.
  • Evans V, Vockler C, Friedlander M, et al. Lacryglobin in human tears, a potential marker for cancer. Clin Exp Ophthalmol. 2001;29:161–163.
  • Böhm D, Keller K, Pieter J, et al. Comparison of tear protein levels in breast cancer patients and healthy controls using a de novo proteomic approach. Oncol Rep. 2012;28:429–438.
  • Lebrecht A, Boehm D, Schmidt M, et al. Diagnosis of breast cancer by tear proteomic pattern. Cancer Genomics Proteomics. 2009;6:177–182.
  • Inubushi S, Kawaguchi H, Mizumoto S, et al. Oncogenic miRNAs identified in tear exosomes from metastatic breast cancer patients. Anticancer Res. 2020;40:3091–3096.

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