Journal of Current Glaucoma Practice

Register      Login

VOLUME 17 , ISSUE 3 ( July-September, 2023 ) > List of Articles


Comparative Proteomic Analysis of the Aqueous Humor from Patients with Pseudoexfoliation Syndrome

Muge Toprak, Nursen Yuksel, Gurler Akpinar, Murat Kasap, Dilara Pirhan, Busra Yilmaz Tugan

Keywords : Apolipoprotein A4, Liver X receptor, Pseudoexfoliation, Retinoid X receptor, Transthyretin

Citation Information : Toprak M, Yuksel N, Akpinar G, Kasap M, Pirhan D, Tugan BY. Comparative Proteomic Analysis of the Aqueous Humor from Patients with Pseudoexfoliation Syndrome. J Curr Glaucoma Pract 2023; 17 (3):118-125.

DOI: 10.5005/jp-journals-10078-1411

License: CC BY-NC 4.0

Published Online: 11-10-2023

Copyright Statement:  Copyright © 2023; The Author(s).


Purpose: The goal of this study was to pinpoint potential molecular pathways that may have contributed to the onset of pseudoexfoliation syndrome (PEX), a systemic illness associated with aging that has no known cause and is brought on by the deposition of fibrillary white flaky debris in ocular tissues. Materials and methods: Protein pools representing each group were created using two-dimensional gel electrophoresis (2DE) in conjunction with a matrix-assisted laser desorption ionization-time of flight/time of flight (MALDI-TOF/TOF) mass spectrometer. Aqueous humor (AH) from patients with PEX and cataracts was also collected for a comprehensive study of the data; ingenuity pathway analysis (IPA) was used for the discovered proteins. Results: In comparison to controls, 2DE showed that 10 sites in PEX patients had differently altered gene expression. Two of these proteins, transthyretin (TTR) and apolipoprotein A4 (ApoA4) were significantly overexpressed in PEX patients, but the remaining proteins were only mildly altered. The liver X receptor (LXR) and the retinoid X receptors (RXR) may play a crucial role in the pathophysiology of PEX according to IPA employing these 10 proteins. Conclusion: The altered proteins, particularly ApoA4 and TTR, may be important in revealing the molecular process behind PEX, as anticipated by IPA.

  1. Vazquez LE, Lee RK. Genomic and proteomic pathophysiology of pseudoexfoliation glaucoma. Int Ophthalmol Clin 2014;54(4):1–13. DOI: 10.1097/IIO.0000000000000047
  2. 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(4):1017–1028. DOI: 10.1039/c1mb05357d
  3. Zenkel M, Schlötzer-Schrehardt U. The composition of exfoliation material and the cells involved in its production. J Glaucoma 2014;23(8 Suppl 1):S12–S14. DOI: 10.1097/IJG.0000000000000123
  4. Pasutto F, Zenkel M, Hoja U, et al. Pseudoexfoliation syndrome-associated genetic variants affect transcription factor binding and alternative splicing of LOXL1. Nat Commun 2017;8:15466. DOI: 10.1038/ncomms15466
  5. Chylack LT Jr, Wolfe JK, Singer DM, et al. The lens opacities classification system III. The longitudinal study of cataract study group. Arch Ophthalmol 1993;111(6):831–836. DOI: 10.1001/archopht.1993.01090060119035
  6. Fautsch MP, Johnson DH. Characterization of myocilin-myocilin interactions. Invest Ophthalmol Vis Sci 2001;42(10):2324–2331.
  7. Ting L, Cowley MJ, Hoon SL, et al. Normalization and statistical analysis of quantitative proteomics data generated by metabolic labeling. Mol Cell Proteomics 2009;8(10):2227–2242. DOI: 10.1074/mcp.M800462-MCP200
  8. Schisterman EF, Vexler A. To pool or not to pool, from whether to when: applications of pooling to biospecimens subject to a limit of detection. Paediatr Perinat Epidemiol 2008;22(5):486–496. DOI: 10.1111/j.1365-3016.2008.00956.x
  9. Berlau J, Lorenz P, Beck R, et al. Analysis of aqueous humour proteins of eyes with and without pseudoexfoliation syndrome. Graefes Arch Clin Exp Ophthalmol 2001;239(10):743–746. DOI: 10.1007/s004170100357
  10. Refetoff S. Thyroid Hormone Serum Transport Proteins. South Dartmouth (MA):, Inc.; 2000.
  11. Beirão JM, Malheiro J, Lemos C, et al. Ophthalmological manifestations in hereditary transthyretin (ATTR V30M) carriers: a review of 513 cases. Amyloid 2015;22(2):117–122. DOI: 10.3109/13506129.2015.1015678
  12. Edward DP, Bouhenni R. Anterior segment alterations and comparative aqueous humor proteomics in the buphthalmic rabbit (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc 2011;109:66–114.
  13. Wakabayashi Y, Kawahara J, Iwasaki T, et al. Retinoic acid transport to lens epithelium in human aqueous humor. Jpn J Ophthalmol 1994;38(4):400–406.
  14. Mehta A, Shapiro MD. Apolipoproteins in vascular biology and atherosclerotic disease. Nat Rev Cardiol 2022;19(3):168–179. DOI: 10.1038/s41569-021-00613-5
  15. Hardenborg E, Botling-Taube A, Hanrieder J, et al. Protein content in aqueous humor from patients with pseudoexfoliation (PEX) investigated by capillary LC MALDI-TOF/TOF MS. Proteomics Clin Appl 2009;3(3):299–306. DOI: 10.1002/prca.200780077
  16. Campos-Peña V, Pichardo-Rojas P, Sánchez-Barbosa T, et al. Amyloid β, lipid metabolism, basal cholinergic system, and therapeutics in Alzheimer's disease. Int J Mol Sci 2022;23(20):12092. DOI: 10.3390/ijms232012092
  17. Reglodi D, Jungling A, Longuespée R, et al. Accelerated pre-senile systemic amyloidosis in PACAP knockout mice - a protective role of PACAP in age-related degenerative processes. J Pathol 2018;245(4):478–490. DOI: 10.1002/path.5100
  18. Turiak L, Kaszás B, Katona K, et al. Localized amyloidosis of the upper aerodigestive tract: complex analysis of the cellular infiltrate and the amyloid mass. Anal Cell Pathol (Amst) 2019;2019:6165140. DOI: 10.1155/2019/6165140
  19. Sharma S, Chataway T, Klebe S, et al. Novel protein constituents of pathological ocular pseudoexfoliation syndrome deposits identified with mass spectrometry. Mol Vis 2018;24:801–817.
  20. Schlötzer-Schrehardt U. Genetics and genomics of pseudoexfoliation syndrome/glaucoma. Middle East Afr J Ophthalmol 2011;18(1):30–36. DOI: 10.4103/0974-9233.75882
  21. Janciauskiene S, Krakau T. Alzheimer's peptide and serine proteinase inhibitors in glaucoma and exfoliation syndrome. Doc Ophthalmol 2003;106(3):215–223. DOI: 10.1023/a:1022949121078
  22. Koliakos GG, Konstas AG, Dimitrakoulias N, et al. Possible role of transferrin in exfoliation syndrome. Acta Ophthalmol Scand 1996;74(2):155–159. DOI: 10.1111/j.1600-0420.1996.tb00061.x
  23. Cumurcu T, Mendil D, Etikan I. Levels of zinc, iron, and copper in patients with pseudoexfoliative cataract. Eur J Ophthalmol 2006;16(4):548–553. DOI: 10.1177/112067210601600408
  24. Delanghe JR, Speeckaert R, Speeckaert MM. Behind the scenes of vitamin D binding protein: more than vitamin D binding. Best Pract Res Clin Endocrinol Metab 2015;29(5):773–786. DOI: 10.1016/j.beem.2015.06.006
  25. Komori H, Watanabe H, Shuto T, et al. α(1)—acid glycoprotein up-regulates CD163 via TLR4/CD14 protein pathway: possible protection against hemolysis-induced oxidative stress. J Biol Chem 2012;287(36):30688–30700. DOI: 10.1074/jbc.M112.353771
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.