Tear Film-specific Biomarkers in Glaucoma Patients

Abstract

Glaucoma is a group of chronic eye diseases that lead to degeneration of retinal ganglion cells (RGCs) and their axons followed by irreversible loss of vision in the patient. Glaucoma is a disease that initially evolves asymptomatically with the first symptoms appearing only at an advanced stage of this eye disease. For this reason, it is always necessary to develop state-of-the-art technologies and methods for the identification and characterization of new, specific biomarkers for the early diagnosis of glaucoma. Therefore, the analysis of biological fluids, as in this case the tear fluid of patients, represents an attractive source to identify new specific as well as sensitive biomarkers in glaucoma. These biomarkers could be involved in the pathophysiological processes of glaucoma or possibly serve for diagnostic differentiation of various types of glaucoma.

Key words

glaucoma - pathology - retina - cornea - intraocular inflammation - nasolacrimal ducts

Publication History

Received: 09 September 2021

Accepted: 04 February 2022

Article published online:
24 February 2022

• Literatur/References

• 1 Li N, Wang N, Zheng J. et al. Characterization of human tear proteome using multiple proteomic analysis techniques. J Proteome Res 2005; 4: 2052-2061
• 2 Filik J, Stone N. Analysis of human tear fluid by Raman spectroscopy. Anal Chim Acta 2008; 616: 177-184
• 3 Perumal N, Funke S, Pfeiffer N. et al. Proteomics analysis of human tears from aqueous-deficient and evaporative dry eye patients. Sci Rep 2016; 6: 29629
• 4 Grus FH, Boehm N, Berneiser S. et al. Analysis of Tear Protein Profiles in Dry-Eye Patients by Mass Spectrometry. Invest Ophthalmol Vis Sci 2009; 50: 2546
• 5 Boehm N, Funke S, Wiegand M. et al. Alterations in the tear proteome of dry eye patients–a matter of the clinical phenotype. Invest Ophthalmol Vis Sci 2013; 54: 2385-2392
• 6 Perumal N, Funke S, Dominik W. et al. In-depth protein profiling and identification of tear fluid biomarkers in different subgroups of dry eye disease: Proline-Rich Protein 4 (PRR4) as a potential biomarker for aqueous-deficient dry eye syndrome. Invest Ophthalmol Vis Sci 2014; 55: 2002
• 7 Shetty R, Ghosh A, Lim RR. et al. Elevated expression of matrix metalloproteinase-9 and inflammatory cytokines in keratoconus patients is inhibited by cyclosporine A. Invest Ophthalmol Vis Sci 2015; 56: 738-750
• 8 Priyadarsini S, Hjortdal J, Sarker-Nag A. et al. Gross cystic disease fluid protein-15/prolactin-inducible protein as a biomarker for keratoconus disease. PLoS One 2014; 9: e113310
• 9 Kolozsvári BL, Petrovski G, Gogolák P. et al. Association between mediators in the tear fluid and the severity of keratoconus. Ophthalmic Res 2014; 51: 46-51
• 10 Holopainen JM, Robciuc A, Cafaro TA. et al. Pro-inflammatory cytokines and gelatinases in climatic droplet keratopathy. Invest Ophthalmol Vis Sci 2012; 53: 3527-3535
• 11 Holopainen JM, Serra HM, Sánchez MC. et al. Altered expression of matrix metalloproteinases and their tissue inhibitors as possible contributors to corneal droplet formation in climatic droplet keratopathy. Acta Ophthalmol 2011; 89: 569-574
• 12 Pieragostino D, Agnifili L, Fasanella V. et al. Shotgun proteomics reveals specific modulated protein patterns in tears of patients with primary open angle glaucoma naïve to therapy. Mol Biosyst 2013; 9: 1108-1116
• 13 Pieragostino D, Bucci S, Agnifili L. et al. Differential protein expression in tears of patients with primary open angle and pseudoexfoliative glaucoma. Mol Biosyst 2012; 8: 1017-1028
• 14 Sommer A. Intraocular Pressure and Glaucoma. Am J Ophthalmol 1989; 107: 186-188
• 15 Aboobakar IF, Johnson WM, Stamer WD. et al. Major review: Exfoliation syndrome; advances in disease genetics, molecular biology, and epidemiology. Exp Eye Res 2017; 154: 88-103
• 16 Gordon MO, Beiser JA, Brandt JD. et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol 2002; 120: 714-720 discussion 829–830
• 17 Roedl JB, Bleich S, Schlötzer-Schrehardt U. et al. Increased homocysteine levels in tear fluid of patients with primary open-angle glaucoma. Ophthalmic Res 2008; 40: 249-256
• 18 Ghaffariyeh A, Honarpisheh N, Shakiba Y. et al. Brain-derived neurotrophic factor in patients with normal-tension glaucoma. Optometry 2009; 80: 635-638
• 19 Shpak AA, Guekht AB, Druzhkova TA. et al. Brain-Derived Neurotrophic Factor in Patients with Primary Open-Angle Glaucoma and Age-related Cataract. Curr Eye Res 2018; 43: 224-231
• 20 Ghaffariyeh A, Honarpisheh N, Heidari MH. et al. Brain-derived neurotrophic factor as a biomarker in primary open-angle glaucoma. Optom Vis Sci 2011; 88: 80-85
• 21 Benraiss A, Chmielnicki E, Lerner K. et al. Adenoviral Brain-Derived Neurotrophic Factor Induces Both Neostriatal and Olfactory Neuronal Recruitment from Endogenous Progenitor Cells in the Adult Forebrain. J Neurosci 2001; 21: 6718-6731
• 22 Zigova T, Pencea V, Wiegand SJ. et al. Intraventricular administration of BDNF increases the number of newly generated neurons in the adult olfactory bulb. Mol Cell Neurosci 1998; 11: 234-245
• 23 Murphy DD, Cole NB, Segal M. Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons. Proc Natl Acad Sci U S A 1998; 95: 11412-11417
• 24 Horch HW, Katz LC. BDNF release from single cells elicits local dendritic growth in nearby neurons. Nat Neurosci 2002; 5: 1177-1184
• 25 Acheson A, Conover JC, Fandl JP. et al. A BDNF autocrine loop in adult sensory neurons prevents cell death. Nature 1995; 374: 450-453
• 26 Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 2001; 24: 677-736
• 27 Lommatzsch M, Zingler D, Schuhbaeck K. et al. The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging 2005; 26: 115-123
• 28 Davarpanah M, Shokri-Mashhadi N, Ziaei R. et al. A systematic review and meta-analysis of association between brain-derived neurotrophic factor and type 2 diabetes and glycemic profile. Sci Rep 2021; 11: 13773
• 29 Phillips HS, Hains JM, Armanini M. et al. BDNF mRNA is decreased in the hippocampus of individuals with Alzheimerʼs disease. Neuron 1991; 7: 695-702
• 30 Scalzo P, Kümmer A, Bretas TL. et al. Serum levels of brain-derived neurotrophic factor correlate with motor impairment in Parkinsonʼs disease. J Neurol 2010; 257: 540-545
• 31 Linker RA, Lee D-H, Demir S. et al. Functional role of brain-derived neurotrophic factor in neuroprotective autoimmunity: therapeutic implications in a model of multiple sclerosis. Brain 2010; 133: 2248-2263
• 32 Bell K, Seigel GM, Pfeiffer N. et al. Up-regulation Of Protein Kinase C Inhibitor (14-3-3) In Retinal Ganglion Cells Incubated With Glaucoma Serum. Invest Ophthalmol Vis Sci 2011; 52: 4598
• 33 Bell K, Wilding C, Funke S. et al. Protective effect of 14-3-3 antibodies on stressed neuroretinal cells via the mitochondrial apoptosis pathway. BMC Ophthalmol 2015; 15: 64
• 34 Wong TT, Zhou L, Li J. et al. Proteomic profiling of inflammatory signaling molecules in the tears of patients on chronic glaucoma medication. Invest Ophthalmol Vis Sci 2011; 52: 7385-7391
• 35 Rossi C, Cicalini I, Cufaro MC. et al. Multi-Omics Approach for Studying Tears in Treatment-Naïve Glaucoma Patients. Int J Mol Sci 2019; 20: 4029
• 36 Vohra R, Dalgaard LM, Vibæk J. et al. Potential metabolic markers in glaucoma and their regulation in response to hypoxia. Acta Ophthalmol 2019; 97: 567-576
• 37 Calandrella N, Seta C de Scarsella G. et al. Carnitine reduces the lipoperoxidative damage of the membrane and apoptosis after induction of cell stress in experimental glaucoma. Cell Death Dis 2010; 1: e62-e62