FEATURES OF THE CONTENT OF PROINFLAMMATORY CYTOKINES IN LACRIMAL AND INTRAOCULAR FLUID IN PATIENTS WITH PRIMARY OPEN-ANGLE GLAUCOMA

Purpose: to study the content of proinflammatory cytokines IL-6, IL-8 and IL-17 in lacrimal and intraocular fluid in patients with advanced stage of primary open-angle glaucoma. Material and methods. The study included 56 patients with advanced stage diagnosis of primary open-angle glaucoma (POAG). The diagnosis was determined by ophthalmological examination, including visual acuity, binocular ophthalmoscopy, spheroperimetry, echoophthalmography, optical coherence tomography, intraocular pressure measurement. The number of men was 21 (37.5 %), women - 35 (62.5 %), the average age of patients was 62.8 ± 4.3 years. Exclusion criteria were acute and exacerbation of chronic inflammatory diseases of the organ of vision, diabetic retinopathy, neovascular glaucoma, uveitis, hemophthalmia, autoimmune and tumor processes of any localization, as well as acute and exacerbations of chronic inflammatory diseases of any organs and systems. Patients who took drugs containing prostaglandins analogues for intraocular pressure normalization, that could activate the inflammatory process, were excluded from the study. A comparison group was composed of 30 patients with the uncomplicated cataract diagnosis. All patients underwent the determination of IL-6, IL-8, IL-17 in the lacrimal and intraocular fluid. Results. It has been established that the significant increase in the concentrations of IL-6, IL-8 and IL-17A in the lacrimal and intraocular fluid was revealed in patients with advanced stage of POAG in comparison with those obtained in patients with uncomplicated cataracts. The obtained data testify to the presence of local destructive-inflammatory process in the mechanisms of the development of primary open-angle glaucoma. The revealed unidirectional change in the concentrations of IL-6 (2.8 times the lacrimal fluid and 5.2 times in the intraocular fluid), IL-8 (1.5 times in the lacrimal fluid and 4 times in the aqueous humor), IL-17 (1.75 times in lacrimal fluid and 1.95 times in the intraocular fluid) allows us to conclude that lacrimal fluid can be used to assess changes in cytokine content in the pathogenesis of ophthalmic diseases.

primary open-angle glaucoma, pro-inflammatory cytokines, intraocular fluid, lacrimal fluid

1. Еричев В.П., Ганковская Л.В., Ковальчук Л.В., Ганковская О.А., Дугина А.Е. Изменение некоторых иммунологических показателей слезной жидкости при избыточном рубцевании после антиглаукоматозных операций у пациентов с первичной открытоугольной глаукомой // Вестн. офтальмологии. 2010. 126. (3). 25-29.

2. Трунов А.Н., Бгатова Н.П., Еремина А.В., Дружинин И.Б., Пожидаева А.А., Трунова Л.А., Черных В.В. Новые подходы к оценке выраженности воспалительных нарушений в патогенезе первичной открытоугольной глаукомы // Аллергология и иммунология. 2016. 17. (2). 107-111.

3. Хохлова А.С., Кириенко А.В., Филина Н.В., Маркелова Е.В. Локальная цитокиновая регуляция на разных стадиях первичной открытоугольной глаукомы // Тихоокеан. мед. журн. 2014. (4). 46-48.

4. Чередниченко Л.П., Барычева Л.Ю., Берновская А.А. Определение провоспалительных цитокинов в ранней диагностике первичной открытоугольной глаукомы // Рос. офтальмол. журн. 2013. 6. (2). 82-85.

5. Черных В.В. Влияние комплексной консервативной терапии на иммунобиохимические показатели в слезной жидкости у пациентов с первичной открытоугольной глаукомой // Глаукома. 2005. (4). 20-24.

6. Черных В.В., Шваюк А.П., Горбенко О.М., Сафронов И.Д., Чехова Т.А., Трунов А.Н., Л.А. Особенности патогенеза начальной и развитой стадии первичной открытоугольной глаукомы // Аллергология и иммунология. 2006. 7. (1). 28-31.

7. Чернявская М.А., Ефремов А.В., Черных В.В. Взаимосвязь цитокинов в слезной и внутриглазной жидкости при меланоме хориоидеи // Вестн. Тамб. ун-та. Сер. Естеств. и техн. науки. 2015. 20. (3). 710-712.

8. Шпак А.А., Гехт А.Б., Дружкова Т.А., Козлова К.И., Гуляева Н.В. Соотношения нейротрофических факторов в слезной жидкости и влаге передней камеры у больных с возрастной катарактой // Офтальмохирургия. 2017. (1). 16-20.

9. Benitez-Del-Castillo Sánchez J., Morillo-Rojas M.D., Galbis-Estrada C., Pinazo-Duran M.D. Determination of inmune response and inflammation mediators in tears: Changes in dry eye and glaucoma as compared to healthy controls // Arch. Soc. Esp. Oftalmol. 2017. 92. (5). 210-217.

10. Carreon T., van der Merwe E., Fellman R.L., Johnstone M., Bhattacharya S.K. Aqueous outflow - A continuum from trabecular meshwork to episcleral veins // Prog. Retin. Eye Res. 2017. 57. 108-133.

11. Chua J., Vania M., Cheung C.M., Ang M., Chee S.P., Yang H., Li J., Wong T.T. Expression profile of inflammatory cytokines in aqueous from glaucomatous eyes // Mol. Vis. 2012. 18. 431-438.

12. Duvesh R., Puthuran G., Srinivasan K., Rengaraj V., Krishnadas S.R., Rajendrababu S., Balakrishnan V., Ramulu P., Sundaresan P1. Multiplex cytokine analysis of aqueous humor from the patients with chronic primary angle closure glaucoma // Curr. Eye Res. 2017. 42. (12). 1608-1613.

13. Huang A.S., Mohindroo C., Weinreb R.N. Aqueous humor outflow structure and function imaging at the bench and bedside: a review // J. Clin. Exp. Ophthalmol. 2016. 7. (4). 578.

14. Huang P., Zhang S.S., Zhang C. The two sides of cytokine signaling and glaucomatous optic neuropathy // J. Ocul. Biol. Dis. Infor. 2009. 2. (2). 78-83.

15. Junglas B., Kuespert S., Seleem A.A., Struller T., Ullmann S., Bösl M., Bosserhoff A., Köstler J., Wagner R., Tamm E.R., Fuchshofer R. Connective tissue growth factor causes glaucoma by modifying the actin cytoskeleton of the trabecular meshwork // Am. J. Pathol. 2012. 180. (6). 2386-2403.

16. Kokubun T., Tsuda S., Kunikata H., Yasuda M., Himori N., Kunimatsu-Sanuki S., Maruyama K., Nakazawa T. Characteristic profiles of inflammatory cytokines in the aqueous humor of glaucomatous eyes // Ocul. Immunol. Inflamm. 2017. 16. 1-12.

17. Lee N.Y., Park H.Y., Park C.K., Ahn M.D. Analysis of systemic endothelin-1, matrix metalloproteinase-9, macrophage chemoattractant protein-1, and high-sensitivity C-reactive protein in normal-tension glaucoma // Curr. Eye Res. 2012. 37. (12). 1121-1126.

18. Song M.M., Lei Y., Wu J.H., Sun X.H. The progress of studies on aqueous humor dynamics abnormality induced by trabecular meshwork and Schlemm canal endothelial cell senescence and its relation with glaucoma // Zhonghua Yan Ke Za Zhi. 2017. 53. (11). 868-873.

19. Taurone S., Ripandelli G., Pacella E., Bianchi E., Plateroti A.M., de Vito S., Plateroti P., Grippaudo F.R., Cavallotti C., Artico M. Potential regulatory molecules in the human trabecular meshwork of patients with glaucoma: immunohistochemical profile of a number of inflammatory cytokines // Mol. Med. Rep. 2015. 11. (2). 1384-1390.

20. Tong Y., Zhou Y.L., Zheng Y., Biswal M., Zhao P.Q., Wang Z.Y. Analyzing cytokines as biomarkers to evaluate severity of glaucoma // Int. J. Ophthalmol. 2017. 10. (6). 925-930.

21. Wang K., Read A.T., Sulchek T., Ethier C.R. Trabecular meshwork stiffness in glaucoma // Exp. Eye Res. 2017. 158. 3-12.

22. Xu S.L., Gao Z.Z., Wang Y., Chen J. Expression of matrix metalloproteinases and inhibitors on the scleral tissue of lamina cribrosa in rat with experimental chronic ocular hypertension // Zhonghua Yan Ke Za Zhi. 2009. 45. (3). 260-265.

23. Yu A.L., Birke K., Moriniere J., Welge-Lüssen U. TGF-beta 2 induces senescence-associated changes in human trabecular meshwork cells // Invest. Ophthalmol. Vis. Sci. 2010. 51. (11). 5718-5723.