Purpose: to investigate the levels of inflammatory and anti-inflammatory cytokines in the aqueous humor and blood plasma of the patients with pseudoexfoliation syndrome (PES). Methods: Inflammatory cytokines (IL-6, IL-10) and anty-inflammatory cytokines (IL-4, IL-8) were measured in ocular fluid samples and blood plasma obtained from patients with PES and cataract (120 eyes), PES and glaucoma (41 eyes), cataract group (45 eyes). The age of patients ranged from 48 to 88 years, an average 65.8 ± 7.1. Patients with systemic diseases and others ocular diseases were excluded. Aspiration of the intraocular fluid was performed using an insulin syringe in a volume of 0.1-0.2 ml. Blood sampling was performed immediately before surgery, and then centrifugation was performed at 3000 rpm. Samples of intraocular fluid and blood serum were immediately frozen at -20.0 and stored until the time of the study. The processing of the results of the study was carried out by the methods of variation and correlation statistics Results: The investigated interleukins were detected in all samples of the anterior chamber aqueous. The level of IL -4 was significantly lower in patients with PES (1,20±0,18) and glaucoma with PES 0,88±0,09 in comparison with cataract group 1,20±0,07 pg/ml. No significant difference in the levels of IL-10 in the ocular fluid of patients was revealed. IL-6 level and IL-10 were significantly higher in anterior chamber aqueous of glaucoma and PES patients in comparison with cataract patients (p<0.05). Various deviations from the control group of proinflammatory and anti-inflammatory cytokines were detected in the the systemic state of cytokines profile. The level of anti-inflammatory IL-4 in the blood serum of PES was increased by 51.7% compared to the control group, while there was no change in the IL-10 level in patients with PES and in combination with glaucoma. Analysis of the level of proinflammatory interleukins in the serum revealed a significant increase in IL - 6 in PES by 18.2%, and in PES and glaucoma - by 48.5% compared to the control group, while the IL - 8 level did not change significantly. Conclusion: The determination of cytokine status in patients with PES and in combination with glaucoma revealed a violation of the local immunological balance, which was manifested by an increase in the activity of pro-inflammatory cytokines (IL-6, IL-8) and a decrease in the activity of anti-inflammatory cytokines (IL-4, IL-10), which reflects deregulatory changes in the immune system and proves the role of local inflammatory-destructive processes in the pathogenesis of PES and glaucoma. The state of systemic cytokine profile in patients with PES and in combination with glaucoma showed an imbalance of interleukins, which was manifested by an increase the level of both pro-inflammatory cytokines (IL-6, IL-8) and anti-inflammatory cytokines (IL-4, IL-10).

Keywords: pseudoexfoliation syndrome, interleukins, ocular fluid

Full text: PDF (Rus) 199K

1. Egorova EV, Borzenok SA, Suskova VS, Eremenko IL. Osobennosti immunnogo reagirovaniya u patsientov s pervichnoy otkrytougolnoy glaukomoy s ispolzovaniem drenazhnykh implantov. Oftalmokhirurgiya. 2015; 3. 13-18. [Russian].
2. Baltatzis S, Georgopoulos G, Theodossiadis P. Fibrin reaction after extracapsular cataract extraction: a statistical evaluation. Eur J Ophthalmol. 1993; 3 (2): 95–7. https://www.ncbi.nlm.nih.gov/pubmed/8353437
3. Chen KH, Wu C, Roy S, Lee S, Liu J. Increased Interleukin-6 in Aqueous Humor of Neovascular Glaucoma. Invest Ophthalmol Vis Sci. 1994; 40: 2627–32. https://www.ncbi.nlm.nih.gov/pubmed/10509659
4. Chua J, Vania M, Gemmy Cheung CM, Ang M, Chee CP, Yang H, Li J, Wong TT. Expression profile of inflammatory cytokines in aqueous from glaucomatous eyes. Mol Vis. 2012; 18: 431–8. https://www.ncbi.nlm.nih.gov/pmc/articles/3283212
5. Funatsu H, Yamashita H, Ikeda T, Mimura T, Eguchi S, Hori S. Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology. 2003; 110 (9): 1690–6. https://www.ncbi.nlm.nih.gov/pubmed/11755841
6. Govetto A, Lorente R, Vázquez de Parga P, Rojas L, Moreno C, Lagoa F, Lorente B. Frequency of pseudoexfoliation among patients scheduled for cataract surgery. J Cataract Refract Surg. 2015 Jun; 41 (6): 1224-31. https://www.ncbi.nlm.nih.gov/pubmed/26100955. https://doi.org/10.1016/j.jcrs.2014.09.039
7. Kopf M, Baumann H, Freer G, Freudenberg M, Lamers M, Kishimoto T, Zinkernagel R, Bluethmann H, Köhler G. Impaired immune and acutephase responses in interleukin-6-defiecient mice. Nature. 1994; 368: 339–42. https://www.ncbi.nlm.nih.gov/pubmed/8127368. https://doi.org/10.1038/368339a0
8. Kovac B, Vukosavljević M, Janićijević MP, Resan M, Janković J. The prevalence of pseudoexfoliation syndrome and possible systemic associations in patients scheduled for cataract surgery at the Military Medical Academy in Belgrade. Vojnosanit Pregl. 2014; 71 (9): 839-44. https://www.ncbi.nlm.nih.gov/pubmed/25282782
9. Ning Dong, Bing Xu, Bingsong Wang, Liqun Chu, and Xin Tang. Aqueous Cytokines as Predictors of Macular Edema in Patients with Diabetes following Uncomplicated Phacoemulsification Cataract Surgery. BioMed Research International. 2015; 2015: 126984. http://dx.doi.org/10.1155/2015/126984.
10. Petrovic MG, Korosec P, Kosnik M, Hawlina M. Vitreous levels of interleukin-8 in patients with proliferative diabetic retinopathy. American Journal of Ophthalmology. 2007; 143 (1): 175–6. https://doi.org/10.1016/j.ajo.2006.07.032
11. Planck SR, Dang TT, Graves D, Tara D, Ansel JC, Rosenbaum JT. Retinal pigment epithelial cells secrete interleukin-6 in response to interleukin-1. Investigative Ophthalmology & Visual Science. 1992; 33: 78–82.
12. Repo LP, Teräsvirta ME, Koivisto KJ. Generalized transluminance of the iris and the frequency of the pseudoexfoliation syndrome in the eyes of transient ischemic attack patients. Ophthalmology. 1993; 100 (3): 352-5. https://www.ncbi.nlm.nih.gov/pubmed/8460005
13. Rubio-Perez JM, Morillas-Ruiz JM. A review: inflammatory process in Alzheimer’s disease, role of cytokines. The Scientific World Journal. 2012; 2012: 756357. https://www.ncbi.nlm.nih.gov/pmc/articles/3330269. https://doi.org/10.1100/2012/756357
14. Sbeity Z, Dorairaj SK, Reddy S, Tello C , Liebmann JM , Ritch R . Ultrasound biomicroscopy of zonular anatomy in clinically unilateral exfoliation syndrome. Acta Ophthalmologica. 2008; 86: 565-8. https://doi.org/10.1111/j.1600-0420.2007.01105.x
15. Silvestre J-S, Mallat Z, Duriez M. Tamarat R, Bureau MF, Scherman D, Duverger N, Branellec D, Tedgui A, Levy BI. Antiangiogenic effect of interleukin-10 in ischemia-induced angiogenesis in mice hindlimb. Circulation Research. 2000; 87 (6): 448–52. https://www.ncbi.nlm.nih.gov/pubmed/10988235. https://doi.org/10.1161/01.RES.87.6.448
16. Scharfenberg E, Schlötzer-Schrehardt U. PSX syndrome. Clinical diagnosis and systemic manifestations. Ophthalmologe. 2012; 109 (10): 952–61. https://www.ncbi.nlm.nih.gov/pubmed/23053333. https://doi.org/10.1007/s00347-012-2534-y
17. Takai Y, Tanito M, Ohira A. Multiplex cytokine analysis of aqueous humor in eyes with primary open-angle glaucoma, exfoliation glaucoma, and cataract. Invest Ophthalmol Vis Sci. 2012; 53 (1): 241–7. https://www.ncbi.nlm.nih.gov/pubmed/22159018. https://doi.org/10.1167/iovs.11-8434
18. Yan SF, Tritto I, Liao H, Liao H, Huang J, Fuller G, Brett J, May L, Stern D. Induction of interleukin-6 (IL-6) by hypoxia in vascular cells. Central role of the binding site for nuclear factor-IL-6. J Biol Chem. 1995; 270: 11463–71. https://www.ncbi.nlm.nih.gov/pubmed/7744784
19. Yildirim Z, Yildirim F, Uçgun Irem N, Sepici-Dinçel A. The role of the cytokines in the pathogenesis of pseudoexfoliation syndrome. Int J Ophthalmol. 2013; 6 (1): 50–3. https://www.ncbi.nlm.nih.gov/pmc/articles/3580249. https://doi.org/10.3980/j.issn.2222-3959.2013.01.10
20. Zenkel M, Lewczuk P, Ju¨nemann A, Kruse FE, Naumann G, Schlo¨tzer-Schrehardt U. Proinflammatory Cytokines Are Involved in the Initiation of the Abnormal Matrix Process in Pseudoexfoliation Syndrome/Glaucoma. The American Journal of Pathology. 2010 june; 176 (6): 2868-79. https://www.ncbi.nlm.nih.gov/pubmed/20395431. https://www.ncbi.nlm.nih.gov/pmc/articles/2877848. https://doi.org/10.2353/ajpath.2010.090914