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Klin Monbl Augenheilkd 2022; 239(02): 169-176
DOI: 10.1055/a-1690-7468
Übersicht

Specific Biomarkers in the Aqueous Humour of Glaucoma Patients

Article in several languages: deutsch | English
Sabrina Reinehr
Experimental Eye Research Institute, Ruhr-Universität Bochum, Deutschland
,
Ana M. Mueller-Buehl
Experimental Eye Research Institute, Ruhr-Universität Bochum, Deutschland
,
Teresa Tsai
Experimental Eye Research Institute, Ruhr-Universität Bochum, Deutschland
,
Stephanie C. Joachim 
Experimental Eye Research Institute, Ruhr-Universität Bochum, Deutschland
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Abstract

Glaucoma, a multifactorial neurodegenerative disease, is the second most common cause of blindness. Since early diagnosis facilitates timely treatment, it is therefore essential to identify appropriate markers. In the future, so-called biomarkers could be helpful in early detection and follow-up. In glaucoma, these parameters could be obtained in the aqueous humour. Altered antibodies, proteins, microRNA (miRNA) and trace element levels have already been identified. This review provides insight into possible changes in the aqueous humour of patients with primary open-angle glaucoma (POAG), normal tension glaucoma (NTG) or pseudoexfoliation glaucoma (PEXG). Studies on antibody changes in POAG patients identified an upregulation of immune system associated antibodies such as heat shock protein (HSP) 27. HSP27 was also upregulated in PEXG patients but decreased in NTG. In POAG and PEXG samples, the levels of certain proteins, including interleukins and endothelin-1, were elevated. The vasoconstrictor endothelin-1 may play a role in regulating intraocular pressure. By contrast, proteins playing a role in the response to oxidative stress were downregulated. In NTG patients, proteins responsible for the elimination of toxic by-products from the respiratory chain were downregulated. In addition, the aqueous humour of POAG and PEXG patients contained several miRNAs that have been linked to tissue development, neurological disease and cellular organisation. Other miRNAs regulated in glaucoma play a role in extracellular matrix remodelling and thus may affect drainage resistance in the trabecular meshwork. It is also interesting to note that the aqueous humour of glaucoma patients showed changes in the levels of trace elements such as zinc and selenium. The elevated zinc levels could be responsible for the imbalance of intraocular matrix metalloproteinases and thus for increased intraocular pressure. All these studies demonstrate the complex changes in aqueous humour in glaucoma. Some of these biomarkers may be useful in the future for early diagnosis of the disease.

Key words

antibodies - aqueous humour - glaucoma - immune system - microRNA - protein - trace elements


Publication History

Received: 30 August 2021

Accepted: 06 November 2021

Article published online:
24 February 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur/References

  • 1 Bonomi L, Marchini G, Marraffa M. et al. Prevalence of glaucoma and intraocular pressure distribution in a defined population. The Egna-Neumarkt Study. Ophthalmology 1998; 105: 209-215
    CrossrefPubMedSearch in Google Scholar
  • 2 Jünemann AGM. [Diagnosis and therapy of pseudoexfoliation glaucoma]. Ophthalmologe 2012; 109: 962-975
    CrossrefPubMedSearch in Google Scholar
  • 3 Dooremal JC. Die Entwicklung der in fremden Grund versetzten lebenden Gewebe. Graefes Arch Clin Exp Ophthalmol 1873; 13: 359-373
    CrossrefPubMedSearch in Google Scholar
  • 4 Augustin AJ. Augenheilkunde. 3., komplett überarb. und erw. Aufl. Berlin, Heidelberg: Springer; 2007
    Search in Google Scholar
  • 5 Streilein JW. Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation. J Leukoc Biol 2003; 74: 179-185
    CrossrefPubMedSearch in Google Scholar
  • 6 Kaplan HJ, Streilein JW. Immune response to immunization via the anterior chamber of the eye. I. F. lymphocyte-induced immune deviation. J Immunol 1977; 118: 809-814
    CrossrefPubMedSearch in Google Scholar
  • 7 Cone RE, Pais R. Anterior Chamber-Associated Immune Deviation (ACAID): An Acute Response to Ocular Insult Protects from Future Immune-Mediated Damage?. Ophthalmol Eye Dis 2009; 1: 33-40
    CrossrefPubMedSearch in Google Scholar
  • 8 Goel M, Picciani RG, Lee RK. et al. Aqueous humor dynamics: a review. Open Ophthalmol J 2010; 4: 52-59
    CrossrefPubMedSearch in Google Scholar
  • 9 Carreon T, van der Merwe E, Fellman RL. et al. Aqueous outflow – A continuum from trabecular meshwork to episcleral veins. Prog Retin Eye Res 2017; 57: 108-133
    CrossrefPubMedSearch in Google Scholar
  • 10 Johnson M, McLaren JW, Overby DR. Unconventional aqueous humor outflow: A review. Exp Eye Res 2017; 158: 94-111
    CrossrefPubMedSearch in Google Scholar
  • 11 Grehn F. Augenheilkunde. 32. Aufl.. Berlin, Heidelberg: Springer; 2020
    Search in Google Scholar
  • 12 Hubens WHG, Mohren RJC, Liesenborghs I. et al. The aqueous humor proteome of primary open angle glaucoma: An extensive review. Exp Eye Res 2020; 197: 108077
    CrossrefPubMedSearch in Google Scholar
  • 13 Leeman M, Choi J, Hansson S. et al. Proteins and antibodies in serum, plasma, and whole blood-size characterization using asymmetrical flow field-flow fractionation (AF4). Anal Bioanal Chem 2018; 410: 4867-4873
    CrossrefPubMedSearch in Google Scholar
  • 14 Gregory MS, Repp AC, Holhbaum AM. et al. Membrane Fas ligand activates innate immunity and terminates ocular immune privilege. J Immunol 2002; 169: 2727-2735
    CrossrefPubMedSearch in Google Scholar
  • 15 Cousins SW, McCabe MM, Danielpour D. et al. Identification of transforming growth factor-beta as an immunosuppressive factor in aqueous humor. Invest Ophthalmol Vis Sci 1991; 32: 2201-2211
    PubMedSearch in Google Scholar
  • 16 Taylor AW. Ocular Immune Privilege and Transplantation. Front Immunol 2016; 7: 37
    CrossrefPubMedSearch in Google Scholar
  • 17 Tripathi RC, Li J, Chan WF. et al. Aqueous humor in glaucomatous eyes contains an increased level of TGF-beta 2. Exp Eye Res 1994; 59: 723-727
    CrossrefPubMedSearch in Google Scholar
  • 18 Acott TS, Kelley MJ. Extracellular matrix in the trabecular meshwork. Exp Eye Res 2008; 86: 543-561
    CrossrefPubMedSearch in Google Scholar
  • 19 Welge-Lussen U, May CA, Lutjen-Drecoll E. Induction of tissue transglutaminase in the trabecular meshwork by TGF-beta1 and TGF-beta2. Invest Ophthalmol Vis Sci 2000; 41: 2229-2238
    PubMedSearch in Google Scholar
  • 20 Joachim SC, Bruns K, Lackner KJ. et al. Antibodies to alpha B-crystallin, vimentin, and heat shock protein 70 in aqueous humor of patients with normal tension glaucoma and IgG antibody patterns against retinal antigen in aqueous humor. Curr Eye Res 2007; 32: 501-509
    CrossrefPubMedSearch in Google Scholar
  • 21 Joachim SC, Wuenschig D, Pfeiffer N. et al. IgG antibody patterns in aqueous humor of patients with primary open angle glaucoma and pseudoexfoliation glaucoma. Mol Vis 2007; 13: 1573-1579
    PubMedSearch in Google Scholar
  • 22 Boehm N, Wolters D, Thiel U. et al. New insights into autoantibody profiles from immune privileged sites in the eye: a glaucoma study. Brain Behav Immun 2012; 26: 96-102
    CrossrefPubMedSearch in Google Scholar
  • 23 Hohberger B, Worn M, Lammer R. et al. Agonistic beta2-Adrenergic Receptor Autoantibodies Characterize the Aqueous Humor of Patients With Primary and Secondary Open-Angle Glaucoma. Front Immunol 2021; 12: 550236
    CrossrefPubMedSearch in Google Scholar
  • 24 Adav SS, Wei J, Terence Y. et al. Proteomic Analysis of Aqueous Humor from Primary Open Angle Glaucoma Patients on Drug Treatment Revealed Altered Complement Activation Cascade. J Proteome Res 2018; 17: 2499-2510
    CrossrefPubMedSearch in Google Scholar
  • 25 Tezel G, Kass MA, Kolker AE. et al. Plasma and aqueous humor endothelin levels in primary open-angle glaucoma. J Glaucoma 1997; 6: 83-89
    CrossrefPubMedSearch in Google Scholar
  • 26 Salvatore S, Vingolo EM. Endothelin-1 role in human eye: a review. J Ophthalmol 2010; 2010: 354645
    CrossrefPubMedSearch in Google Scholar
  • 27 Choritz L, Machert M, Thieme H. Correlation of endothelin-1 concentration in aqueous humor with intraocular pressure in primary open angle and pseudoexfoliation glaucoma. Invest Ophthalmol Vis Sci 2012; 53: 7336-7342
    CrossrefPubMedSearch in Google Scholar
  • 28 Grus FH, Joachim SC, Sandmann S. et al. Transthyretin and complex protein pattern in aqueous humor of patients with primary open-angle glaucoma. Mol Vis 2008; 14: 1437-1445
    PubMedSearch in Google Scholar
  • 29 Kaeslin MA, Killer HE, Fuhrer CA. et al. Changes to the Aqueous Humor Proteome during Glaucoma. PLoS One 2016; 11: e0165314
    CrossrefPubMedSearch in Google Scholar
  • 30 Hubens WHG, Beckers HJM, Gorgels T. et al. Increased ratios of complement factors C3a to C3 in aqueous humor and serum mark glaucoma progression. Exp Eye Res 2021; 204: 108460
    CrossrefPubMedSearch in Google Scholar
  • 31 Kodeboyina SK, Lee TJ, Bollinger K. et al. Aqueous Humor Proteomic Alterations Associated with Visual Field Index Parameters in Glaucoma Patients: A Pilot Study. J Clin Med 2021; 10: 1180
    CrossrefPubMedSearch in Google Scholar
  • 32 Chono I, Miyazaki D, Miyake H. et al. High interleukin-8 level in aqueous humor is associated with poor prognosis in eyes with open angle glaucoma and neovascular glaucoma. Sci Rep 2018; 8: 14533
    CrossrefPubMedSearch in Google Scholar
  • 33 Nassiri N, Nassiri N, Majdi M. et al. Erythropoietin levels in aqueous humor of patients with glaucoma. Mol Vis 2012; 18: 1991-1995
    PubMedSearch in Google Scholar
  • 34 Yavrum F, Elgin U, Kocer ZA. et al. Evaluation of aqueous humor and serum clusterin levels in patients with glaucoma. BMC Ophthalmol 2021; 21: 25
    CrossrefPubMedSearch in Google Scholar
  • 35 He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004; 5: 522-531
    CrossrefPubMedSearch in Google Scholar
  • 36 Mitchell PS, Parkin RK, Kroh EM. et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 2008; 105: 10513-10518
    CrossrefPubMedSearch in Google Scholar
  • 37 Inoue T, Kawaji T, Tanihara H. Elevated levels of multiple biomarkers of Alzheimerʼs disease in the aqueous humor of eyes with open-angle glaucoma. Invest Ophthalmol Vis Sci 2013; 54: 5353-5358
    CrossrefPubMedSearch in Google Scholar
  • 38 Liu Y, Chen Y, Wang Y. et al. microRNA Profiling in Glaucoma Eyes With Varying Degrees of Optic Neuropathy by Using Next-Generation Sequencing. Invest Ophthalmol Vis Sci 2018; 59: 2955-2966
    CrossrefPubMedSearch in Google Scholar
  • 39 Dunmire JJ, Lagouros E, Bouhenni RA. et al. MicroRNA in aqueous humor from patients with cataract. Exp Eye Res 2013; 108: 68-71
    CrossrefPubMedSearch in Google Scholar
  • 40 Kanehisa M, Araki M, Goto S. et al. KEGG for linking genomes to life and the environment. Nucleic Acids Res 2008; 36: D480-D484
    CrossrefPubMedSearch in Google Scholar
  • 41 Tanaka Y, Tsuda S, Kunikata H. et al. Profiles of extracellular miRNAs in the aqueous humor of glaucoma patients assessed with a microarray system. Sci Rep 2014; 4: 5089
    CrossrefPubMedSearch in Google Scholar
  • 42 Jayaram H, Phillips JI, Lozano DC. et al. Comparison of MicroRNA Expression in Aqueous Humor of Normal and Primary Open-Angle Glaucoma Patients Using PCR Arrays: A Pilot Study. Invest Ophthalmol Vis Sci 2017; 58: 2884-2890
    CrossrefPubMedSearch in Google Scholar
  • 43 Bradley JM, Vranka J, Colvis CM. et al. Effect of matrix metalloproteinases activity on outflow in perfused human organ culture. Invest Ophthalmol Vis Sci 1998; 39: 2649-2658
    PubMedSearch in Google Scholar
  • 44 Drewry MD, Challa P, Kuchtey JG. et al. Differentially expressed microRNAs in the aqueous humor of patients with exfoliation glaucoma or primary open-angle glaucoma. Hum Mol Genet 2018; 27: 1263-1275
    CrossrefPubMedSearch in Google Scholar
  • 45 Wołonciej M, Milewska E, Roszkowska-Jakimiec W. Trace elements as an activator of antioxidant enzymes. Postepy Hig Med Dosw (Online) 2016; 70: 1483-1498
    CrossrefPubMedSearch in Google Scholar
  • 46 Akyol N, Deger O, Keha EE. et al. Aqueous humour and serum zinc and copper concentrations of patients with glaucoma and cataract. Br J Ophthalmol 1990; 74: 661-662
    CrossrefPubMedSearch in Google Scholar
  • 47 Hohberger B, Chaudhri MA, Michalke B. et al. Levels of aqueous humor trace elements in patients with open-angle glaucoma. J Trace Elem Med Biol 2018; 45: 150-155
    CrossrefPubMedSearch in Google Scholar
  • 48 Lillico A, Jacobs B, Reid M. Selenium Supplementation and Risk of Glaucoma in the NPC trial [Dissertation]. Tucson, AZ: Arizona Cancer Center, University of Arizona; 2002
    PubMedSearch in Google Scholar
  • 49 Bruhn RL, Stamer WD, Herrygers LA. et al. Relationship between glaucoma and selenium levels in plasma and aqueous humor. Br J Ophthalmol 2009; 93: 1155-1158
    CrossrefPubMedSearch in Google Scholar
  • 50 Jünemann AGM, Michalke B, Lucio M. et al. Aqueous humor selenium level and open-angle glaucoma. J Trace Elem Med Biol 2018; 50: 67-72
    CrossrefPubMedSearch in Google Scholar