Tear fluid as a source of biomarkers for the neurodegeneration in central nervous system
https://doi.org/10.30629/2658-7947-2023-28-5-5-13
Abstract
Composition of tear fluid alter not only in ocular diseases but in systemic pathologic processes including central nervous system (CNS) disorders. It is due to the variety of regulatory pathways for the tear production with active participation of CNS. The review represent data about mechanisms of tear production regulation, sources of metabolites present in tears, alterations of tear fluid composition in Alzheimer’s and Parkinson diseases, multiple sclerosis and amyotrophic lateral sclerosis. These neurodegenerative diseases are accompanied by typical alteration of concentrations of different protein bioregulators (cytokines, growth factors, synucleins, etc.) and catecholamines. These alterations often correlate with ones in cerebrospinal fluid appearing even before the clinical manifestation of the disease. Thus tear fluid analyses is a promising non-invasive method for the early diagnostic, prognosis and monitoring of neurodegenerative diseases, and also for the personalized therapy. We tried to represent the most recent data because interest to this problem has increased during the last years, and our own data also.
About the Authors
N. B. Chesnokova
Helmholtz National Medical Research Center of Eye Diseases
Russian Federation
Russian Federation
Natalya B. Chesnokova
Moscow.
T. A. Pavlenko
Helmholtz National Medical Research Center of Eye Diseases
Russian Federation
Russian Federation
Moscow.
O. V. Beznos
Helmholtz National Medical Research Center of Eye Diseases
Russian Federation
Russian Federation
Moscow.
M. R. Nodel
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Russian Federation
Moscow.
References
1. Marchesi N., Fahmideh F., Boschi F., Pascale A., Barbieri A. Ocular Neurodegenerative Diseases: Interconnection between Retina and Cortical Areas. Cells. 2021;10(9):2394. https://doi.org/10.3390/cells10092394
2. Ohno Y., Yako T., Satoh K., Nagase H., Shitara A., Hara H., Kashimata M. Retinal damage alters gene expression profile in lacrimal glands of mice. J Pharmacol. Sci. 2022;149(1):20–26. https://doi.org/10.1016/j.jphs.2022.02.007
3. Safonova T.N., Pateiuk L.S. Ocular surface system integrity. Vestnik Oftalmologii. 2015;131(1):96–103. (In Russ.). https://doi.org/10.17116/oftalma2015131196-102
4. Bründl M., Garreis F., Schicht M., Dietrich J., Paulsen F. Characterization of the innervation of the meibomian glands in humans, rats and mice. Annals of Anatomy, 2021;233:151609. https://doi.org/10.1016/j.aanat.2020.151609
5. Knop N., Knop E. Conjunctiva-associated lymphoid tissue in the human eye. Invest. Ophthalmol. Vis. Sci. 2000;41(6):1270–1279.
6. Dartt D.A. Neural regulation of lacrimal gland secretory processes: relevance in dry eye diseases. Progress in Retinal and Eye Research. 2009;28(3):155–177. https://doi.org/10.1016/j.preteyeres.2009.04.003
7. Dartt D.A. Signal transduction and control of lacrimal gland protein secretion: a review. Curr. Eye Res. 1989;8:619–636.
8. Dias-Teixeira K. Lacrimal Gland Postganglionic Innervation: Unveiling the Role of Parasympathetic and Sympathetic Nerves in Stimulating Tear Secretion. Am. J. Pathol. 2020;190(5):968–969. https://doi.org/10.1016/j.ajpath.2020.03.001
9. Berczeli O., Szarka D., Elekes G., Vizvári E., Szalay L., Almássy J., Tálosi L., Ding C., Tóth-Molnár E. The regulatory role of vasoactive intestinal peptide in lacrimal gland ductal fluid secretion: A new piece of the puzzle in tear production. Molecular Vision. 2020;26:780–788.
10. Li D., Jiao J., Shatos M.A., Hodges R.R., Dartt D.A. Effect of VIP on intracellular [Ca2+], extracellular regulated kinase 1/2, and secretion in cultured rat conjunctival goblet cells. Invest. Ophthalmol. .Vis. Sci. 2013;54(4):2872–2884. https://doi.org/10.1167/iovs.12-11264
11. Martin X.D., Brennan M.C. Dopamine and its metabolites in human tears. Eur. J. Ophthalmol. 1993;3(2):83–8.
12. Sharma N.S., Acharya S.K., Nair A.P., Matalia J., Shetty R., Ghosh A., Sethu S. Dopamine levels in human tear fluid. Ind. J. Ophthalmol. 2019;67(1):38–41. https://doi.org/10.4103/ijo.IJO_568_18
13. Ji Y.W., Kang H.G., Song J.S., Jun J.W., Han K., Kim T.I., Seo K.Y., Lee H.K. The Dopaminergic Neuronal System Regulates the Inflammatory Status of Mouse Lacrimal Glands in Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2021;62(4):14. https://doi.org/10.1167/iovs.62.4.14
14. Cox S.M., Nichols J.J. The neurobiology of the meibomian glands. Ocular Surface. 2014;12(3):167–177. https://doi.org/10.1016/j.jtos.2014.01.005
15. Murakami T., Nakamura M., Fujihara T., Nakata K. Involvement of dopamine D1-like receptors in mediating increases in protein secretion from rabbit lacrimal gland. Journal of Ocular Pharmacology and Therapeutics. 1999;15(5):447–454. https://doi.org/10.1089/jop.1999.15.447
16. Imada T., Nakamura S., Hisamura R., Izuta Y., Jin K., Ito M., Kitamura N., Tanaka K.F., Mimura M., Shibuya I., Tsubota K. Serotonin hormonally regulates lacrimal gland secretory function via the serotonin type 3a receptor. Scientific Reports. 2017;7(1):6965. https://doi.org/10.1038/s41598-017-06022-4
17. Dartt D.A. Interaction of EGF family growth factors and neurotransmitters in regulating lacrimal gland secretion. Exp. Eye Res. 2004;78(3):337–3345. https://doi.org/10.1016/s0014-4835(03)00202-1
18. Trachtman J.N. Vision and the hypothalamus. Optometry. 2010;81(2):100–115. https://doi.org/10.1016/j.optm.2009.07.016
19. Ham B.M., Jacob J.T., Cole R.B. Single eye analysis and contralateral eye comparison of tear proteins in normal and dry eye model rabbits by MALDI-ToF mass spectrometry using waxcoated target plates. Anallytical and Bioanalytical Chemistry. 2007;387(3):889–900.
20. Kurenkov V.V., Kashnikova O.A., Polunin G.S., Sheludchenko V.M., Beznos O.V., Chesnokova N.B. Influence of specialized lazer keratomileusis on the concentration of potassium ions in the tear fluid. Vestnik Oftalmologii 2001;117(1):36–38. (In Russ.).
21. Gundorova R.A., Makarov P.V., Chesnokova N.B., Beznos O.V. Vliyanie odnostoronnei keratoplastiki na zajivlenije rogovitsy parnogo glasa pri dvustoronnikh ojogah. Vserossijskaya nauchno-prakticheskaya konferenzija ‘Novyje technologii v lechenii zabolevanij rogovitsy’. 2004:108–110. (In Russ.)]. ISBN:5-900836-25-8
22. Neroeva N.V., Chesnokova N.B., Katargina L.A., Pavlenko T.A., Beznos O.V., Ilyukhin P.A., Utkina O.A. Changes of Alpha-2-Macroglobulin Activity in Tears in Experimental Retinal Pigment Epithelium Atrophy in Rabbit. Russian Ophthalmological Journal. 2022;15(3):112–117. (In Russ.). https://doi.org/10.21516/2072-0076-2022-15-3-112-117
23. Romaus-Sanjurjo D., Regueiro U., López-López M., Vázquez-Vázquez L., Ouro A., Lema I., Sobrino T. Alzheimer’s Disease Seen through the Eye: Ocular Alterations and Neurodegeneration. Int. J. Mol. Sci. 2022;23(5):2486. https://doi.org/10.3390/ijms23052486
24. Czakó C., Kovács T., Ungvari Z., Csiszar A., Yabluchanskiy A., Conley S., Csipo T., Lipecz A., Horváth H., Sándor G.L., István L., Logan T., Nagy Z.Z., Kovács I. Retinal biomarkers for Alzheimer’s disease and vascular cognitive impairment and dementia (VCID): implication for early diagnosis and prognosis. Geroscience. 2020;42(6):1499–1525. https://doi.org/10.1007/s11357-020-00252-7
25. Örnek N., Dağ E., Örnek K. Corneal Sensitivity and Tear Function in Neurodegenerative Diseases. Curr. Eye Res. 2015;40(4):423–428. https://doi.org/10.3109/02713683.2014.930154
26. Roda M., Ciavarella C., Giannaccare G., Versura P. Biomarkers in Tears and Ocular Surface: A Window for Neurodegenerative Diseases. Eye and Contact Lens. 2020;46(Suppl. S2):S129–S134. https://doi.org/10.1097/ICL.0000000000000663
27. Gijs M., Ramakers I.H.G.B., Visser P.J., Verhey F.R.J., van de Waarenburg M.P.H., Schalkwijk C.G., Nuijts R.M.M.A., Webers C.A.B. Association of tear fluid amyloid and tau levels with disease severity and neurodegeneration. Sci. Rep. 2021;11(1):22675. https://doi.org/10.1038/s41598-021-01993-x
28. Gijs M., Nuijts R.M., Ramakers I., Verhey F., Webers C.A.B. Differences in Tear Protein Biomarkers between Patients with Alzheimer’s Disease and Controls. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1744.
29. Kalló G., Emri M., Varga Z., Ujhelyi B., Tozsér J., Csutak A., Csosz É. Changes in the Chemical Barrier Composition of Tears in Alzheimer’s Disease Reveal Potential Tear Diagnostic Biomarkers. PLoS ONE. 2016;11(6):e0158000. https://doi.org/10.1371/journal.pone.0158000
30. Kenny A., Jiménez-Mateos E.M., Zea-Sevilla M.A., Rábano A., Gili-Manzanaro P., Prehn J.H.M., Henshall D.C., Ávila J., Engel T., Hernández F. Proteins and MicroRNAs Are Differentially Expressed in Tear Fluid from Patients with Alzheimer’s Disease. Sci. Rep. 2019;9(1):15437. https://doi.org/10.1038/s41598-019-51837-y
31. Higaki S., Muramatsu M., Matsuda A., Matsumoto K., Satoh J., Michikawa M., Niida S. Defensive effect of microRNA-200b/c against amyloid-beta peptide-induced toxicity in Alzheimer’s disease models. PLoS One. 2018;13(5):e0196929. https://doi.org/10.1371/journal.pone.0196929
32. Del Prete S., Marasco D., Sabetta R.S. , Del Prete А., Zito Marino F., Franco R., Troisi S., Troisi M., Cennamo G. Tear Liquid for Predictive Diagnosis of Alzheimer’s Disease. Sci. Rep. 2021;4:26. https://doi.org/10.3390/reports4030026
33. Chesnokova N.B., Pavlenko T.A., Ugrumov M.V. Ophthalmic disorders as a manifestation of Parkinson’s disease. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2017;117(9):124–131. (In Russ.). https://doi.org/10.17116/jnevro201711791124-131
34. Zhang Y., Zhang X., Yue Y., Tian T. Retinal Degeneration: A Window to Understand the Origin and Progression of Parkinson’s Disease? Front. Neurosci. 2022;15:799526. https://doi.org/10.3389/fnins.2021.799526
35. Nowacka B., Lubinski W., Honczarenko K., Potemkowski A., Safranow K. Ophthalmological features of Parkinson disease. Med. Sci. Monit. 2014;20:2243–2249. https://doi.org/10.12659/MSM.890861
36. Bayer A.U., Ferrari F., Erb C. High occurrence rate of glaucoma among patients with Alzheimer’s disease. Eur. Neurol. 2002;47(3):165–168. https://doi.org/10.1159/000047976
37. Ulusoy E.K., Ulusoy D.M. Evaluation of corneal sublayers thickness and corneal parameters in patients with Parkinson’s disease. Int. J. Neurosci. 2021;131(10):939–945. https://doi.org/10.1080/00207454.2020.1761353
38. Tamer C., Melek I.M., Duman T., Oksüz H. Tear film tests in Parkinson’s disease patients. Ophthalmology. 2005;112(10):1795. https://doi.org/10.1016/j.ophtha.2005.04.025
39. Boerger M., Funke S., Leha A., Roser A.E., Wuestemann A.K., Maass F., Bähr M., Grus F., Lingor P. Proteomic analysis of tear fluid reveals disease-specific patterns in patients with Parkinson’s disease — A pilot study. Parkinsonism Related Disorders. 2019;63:3–9. https://doi.org/10.1016/j.parkreldis.2019.03.001
40. Acera A., Gómez-Esteban J.C., Murueta-Goyena A., Galdos M., Azkargorta M., Elortza F., Ruzafa N., Ibarrondo O., Pereiro X., Vecino E. Potential Tear Biomarkers for the Diagnosis of Parkinson’s Disease-A Pilot Study. Proteomes. 2022;10(1):4. https://doi.org/10.3390/proteomes10010004
41. Çomoglu S.S., Güven H., Acar M., Ozturk G., Koçer B. Tear levels of tumor necrosis factoralpha in patients with Parkinson’s disease. Neuroscience Letters. 2013;553:63–67. https://doi.org/10.1016/j.neulet.2013.08.019
42. Magalhães P., Lashuel H.A. Opportunities and challenges of alpha-synuclein as a potential biomarker for Parkinson’s disease and other synucleinopathies. NPJ Parkinson’s Disease. 2022;8(1):93. https://doi.org/10.1038/s41531-022-00357-0
43. Anderson J., Walker D.E., Goldstein J.M. de Laat R., Banducci K., Caccavello R.J., Barbour R., Huang J., Kling K., Lee M., Diep L., Keim P.S., Shen X., Chataway T., Schlossmacher M.G., Seubert P., Schenk D., Sinha S., Gai W.P., Chilcote T.J. Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J. Biol. Chem. 2006;281(40):29739–29752. https://doi.org/10.1074/jbc.M600933200
44. Ortuño-Lizarán I., Beach T.G., Serrano G.E., Walker D.G., Adler C.H., Cuenca N. Phosphorylated α-synuclein in the retina is a biomarker of Parkinson’s disease pathology severity. Movement Disorders. 2018;33(8):1315–1324. https://doi.org/10.1002/mds.27392
45. Malek N., Swallow D., Grosset K.A., Anichtchik O., Spillantini M., Grosset D.G. Alpha-synuclein in peripheral tissues and body fl uids as a biomarker for Parkinson’s disease — a systematic review. Acta Neurol. Scand. 2014;130(2):59–72. https://doi.org/10.1111/ane.12247
46. Hamm-Alvarez S.F., Okamoto C.T., Janga S.R., Feigenbaum D., Edman M.C., Freire D., Shah M., Ghanshani R., Mack W.J., Lew M.F. Oligomeric a-synuclein is increased in basal tears of Parkinson’s patients. Biomarkers in Medicine. 2019;13:941–952. https://doi.org/10.2217/bmm-2019-0167
47. Edman M.C., Janga S.R., Kakan S.S., Okamoto C.T., Freire D., Feigenbaum D., Lew M., Hamm-Alvarez S.F. Tears — more to them than meets the eye: why tears are a good source of biomarkers in Parkinson’s disease. Biomarkers in Medicine. 2020;14(2):151–163. https://doi.org/10.2217/bmm-2019-0364
48. Lin C.W., Lai T.T., Chen S.J., Lin C.H. Elevated α-synuclein and NfL levels in tear fl uids and decreased retinal microvascular densities in patients with Parkinson’s disease. Geroscience. 2022;44(3):1551–1562. https://doi.org/10.1007/s11357-022-00576-6
49. Magalhães P., Lashuel H.A. Opportunities and challenges of alpha-synuclein as a potential biomarker for Parkinson’s disease and other synucleinopathies. NPJ Parkinson’s Disease. 2022;8(1):93. https://doi.org/10.1038/s41531-022-00357-0
50. Kim A.R., Nodel M.R., Pavlenko T.A., Chesnokova N.B., Yakhno N.N., Ugrumov M.V. Tear Fluid Catecholamines As Biomarkers of the Parkinson’s Disease: A Clinical and Experimental Study. Acta Naturae. 2019;11(4):99–103. (In Puss.). https://doi.org/10.32607/20758251-2019-11-4-99-103
51. Bogdanov V., Kim A., Nodel M., Pavlenko T., Pavlova E., Blokhin V., Chesnokova N., Ugrumov M. A Pilot Study of Changes in the Level of Catecholamines and the Activity of α-2-Macroglobulin in the Tear Fluid of Patients with Parkinson’s Disease and Parkinsonian Mice. Int. J. Mol. Sci. 2021;22(9):4736. https://doi.org/10.3390/ijms22094736
52. Rehman A.A., Ahsan H., Khan F.H. α-2-Macroglobulin: A physiological guardian. J. Cell. Phys. 2013;228:1665–1675. https://doi.org/10.1002/jcp.24266
53. Parisi V., Manni G., Spadaro M., Colacino G., Restuccia R., Marchi S., Bucci M.G., Pierelli F. Correlation between morphological and functional retinal impairment in multiple sclerosis patients. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2520–2527.
54. Gordon-Lipkin E., Chodkowski B., Reich D.S., Smith S.A., Pulicken M., Balcer L.J., Frohman E.M., Cutter G., Calabresi P.A. Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis. Neurology. 2007;69(16):1603–1609. https://doi.org/10.1212/01.wnl.0000295995.46586.ae
55. Thompson A.J., Banwell B.L., Barkhof F., Carroll W.M., Coetzee T., Comi G., Correale J., Fazekas F., Filippi M., Freedman M.S., Fujihara K., Galetta S.L., Hartung H.P., Kappos L., Lublin F.D., Marrie R.A., Miller A.E., Miller D.H., Montalban X., Mowry E.M., Sorensen P.S., Tintoré M., Traboulsee A.L., Trojano M., Uitdehaag B.M.J., Vukusic S., Waubant E., Weinshenker B.G., Reingold S.C., Cohen J.A. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurology. 2018;17(2):162–173. https://doi.org/10.1016/S1474-4422(17)30470-2
56. Calais G., Forzy G., Crinquette C., Mackowiak A., de Seze J., Blanc F., Lebrun C., Heinzlef O., Clavelou P., Moreau T., Hennache B., Zephir H., Verier A., Neuville V., Confavreux C., Vermersch P., Hautecoeur P. Tear analysis in clinically isolated syndrome as new multiple sclerosis criterion. Multiple Sclerosis. 2010;16(1):87–92. https://doi.org/10.1177/1352458509352195
57. Hümmert M.W., Wurster U., Bönig L., Schwenkenbecher P., Sühs K.W., Alvermann S., Gingele S., Skripuletz T., Stangel M. Investigation of Oligoclonal IgG Bands in Tear Fluid of Multiple Sclerosis Patients. Front. Immunol. 2019;10:1110. https://doi.org/10.3389/fi mmu.2019.01110
58. Pieragostino D., Lanuti P., Cicalini I., Cufaro M.C., Ciccocioppo F., Ronci M., Simeone P., Onofrj M., van der Pol E., Fontana A., Marchisio M., Del Boccio P. Proteomics characterization of extracellular vesicles sorted by flow cytometry reveals a disease-specific molecular cross-talk from cerebrospinal fluid and tears in multiple sclerosis. J. Proteom. 2019;204:103403. https://doi.org/10.1016/j.jprot.2019.103403
59. Cicalini I., Rossi C., Pieragostino D., Agnifili L., Mastropasqua L., di Ioia M., De Luca G., Onofrj M., Federici L., Del Boccio P. Integrated Lipidomics and Metabolomics Analysis of Tears in Multiple Sclerosis: An Insight into Diagnostic Potential of Lacrimal Fluid. Int. J. Mol. Sci. 2019;20(6):1265. https://doi.org/10.3390/ijms20061265
60. Salvisberg C., Tajouri N., Hainard A., Burkhard P.R., Lalive P.H., Turck N. Exploring the human tear fluid: discovery of new biomarkers in multiple sclerosis. Proteomics Clin. Appl. 2014;8(3–4):185–194. https://doi.org/10.1002/prca.201300053
61. Fu J., He J., Zhang Y., Liu Z., Wang H., Li J., Chen L., Fan D. Small fiber neuropathy for assessment of disease severity in amyo trophic lateral sclerosis: corneal confocal microscopy findings. Orphanet J. Rare Dis. 2022;17(1):7. https://doi.org/10.1186/s13023-021-02157-w
62. Cennamo G., Montorio D., Ausiello F.P., Magno L., Iodice R., Mazzucco A., Iuzzolino V.V., Senerchia G., Brescia Morra V., Nolano M., Costagliola C., Dubbioso R. Correlation between Retinal Vascularization and Disease Aggressiveness in Amyotrophic Lateral Sclerosis. Biomedicines. 2022;10(10):2390. https://doi.org/10.3390/biomedicines10102390
63. Ami D., Duse A., Mereghetti P., Cozza F., Ambrosio F., Ponzini E., Grandori R., Lunetta C., Tavazzi S., Pezzoli F., Natalello A. Tear-Based Vibrational Spectroscopy Applied to Amyotrophic Lateral Sclerosis. Analytical Chemistry. 2021;93(51):16995–17002. https://doi.org/10.1021/acs.analchem.1c02546
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Chesnokova N.B., Pavlenko T.A., Beznos O.V., Nodel M.R. Tear fluid as a source of biomarkers for the neurodegeneration in central nervous system. Russian neurological journal. 2023;28(5):5-13. (In Russ.) https://doi.org/10.30629/2658-7947-2023-28-5-5-13
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