Офтальмохирургия. 2019; : 13-17
Особенности содержания трансформирующих факторов роста – бета 1,2,3 (TGF-β1, TGF-β2, TGF-β3) во внутриглазной жидкости при первичной открытоугольной глаукоме
https://doi.org/10.25276/0235-4160-2019-2-13-17Аннотация
Цель. Изучить содержание трансформирующих фактора роста – бета 1,2,3 (TGF-β1, TGF-β2, TGF-β3) во внутриглазной жидкости пациентов с развитой стадией первичной открытоугольной глаукомы.
Материал и методы. Были обследованы 50 пациентов с верифицированным, на основании офтальмологического обследования, диагнозом развитой стадии первичной открытоугольной глаукомы (ПОУГ), которые составили основную группу. Контрольную группу составили 30 пациентов с диагнозом неосложненной катаракты. Концентрацию изоформ трансформирующего фактора роста – бета определяли с использованием набора Bio-Plex Pro™ TGF-β 3-plex Assay методом проточной флюорометрии на двухлучевом лазерном анализаторе Bio-Plex 200, Bio-Rad, США. Во внутриглазной жидкости одномоментно определялись 3 изоформы (TGF-β1, TGF-β2, TGF-β3).
Результаты. В результате проведенного исследования было установлено достоверное нарастание концентраций во внутриглазной жидкости пациентов с развитой стадией первичной открытоугольной глаукомы в сравнении с данными исследований внутриглазной жидкости лиц с неосложненной катарактой – TGF-β1 (более чем 3 раза), TGF-β2 (в 1,4 раза) и TGF-β3 (более чем 6 раз). Были выявлены прямые достоверные коррелятивные взаимосвязи между TGF-β1 и TGF-β2 (r=0,41, p<0,03), между TGF-β1 и TGF-β3 (r=0,83, p<0,004 ) и между TGF-β2 и TGF-β3 (r=0,35, p<0,04).
Заключение. Установленное сопряженное нарастание концентраций изучаемых представителей суперсемейства трансформирующих факторов роста-бета, обладающих противовоспалительной активностью, способностью стимулировать процессы пролиферации, клеточного роста, синтез белков внеклеточного матрикса и др., свидетельствует об их значимости в механизмах развития ПОУГ.
Список литературы
1. Трунов А.Н., Бгатова Н.П., Еремина А.В. и др. Новые подходы к оценке выраженности воспалительных нарушений в патогенезе первичной открытоугольной глаукомы. Аллергология и иммунология. 2016;17(2): 107-111.
2. Черных В.В., Бгатова Н.П., Ермакова О.В. и др. Местный воспалительный процесс как возможное проявление нарушений увеолимфатического оттока внутриглазной жидкости при глаукоме. Ч. 2. Национальный журнал глаукома. 2018;17(2): 3-11.
3. Carreon T., van der Merwe E., Fellman R.L. et al. Aqueous outflow – A continuum from trabecular meshwork to episcleral veins. Prog. Retin. Eye Res. 2017;57: 108-133. Available from: doi.org/10.1016/j.preteyeres.2016.12.004.
4. 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. Available from: doi.org/10.4172/2155-9570.1000578.
5. Junglas B., Kuespert S., Seleem A.A. et al. Connective tissue growth factor causes glaucoma by modifying the actin cytoskeleton of the trabecular meshwork. Am. J. Pathol. 2012;180(6): 2386-2403. Available from: doi.org/10.1016/j.ajpath.2012.02.030.
6. 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 highsensitivity C-reactive protein in normal-tension glaucoma. J. Ophthalmology. 2016;2016. Available from: http://dx.doi.org/10.1155/2016/2678017.
7. 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.
8. Taurone S., Ripandelli G., Pacella E. et al. 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. Available from: doi.org/10.3892/mmr.2014.2772.
9. Wang K., Read A.T., Sulchek T., Ethier C.R. Trabecular meshwork stiffness in glaucoma. Exp. Eye. Res. 2017;158: 3-12. Available from: doi.org/10.1016/j.exer.2016.07.011.
10. Черных В.В., Шваюк А.П., Горбенко О.М. и др. Особенности патогенеза начальной и развитой стадии первичной открытоугольной глаукомы. Аллергология и иммунология. 2006;7(1): 28-31.
11. Chua J., Vania M., Cheung C.M. et al. Expression profile of inflammatory cytokines in aqueous from glaucomatous eyes. Mol. Vis. 2012;18: 431-438.
12. Duvesh R., Puthuran G., Srinivasan K.et al. Multiplex cytokine analysis of aqueous humor from the patients with chronic primary angle closure glaucoma. Curr. Eye Res. 2017;42(12): 1608-1613. Available from: doi.org/10.1080/02713683.2017.1362003.
13. Huang P., Zhang S.S., Zhang C. Erratum: The two sides of cytokine signaling and glaucomatous optic neuropathy. J. Ocul. Biol. Dis. Infor. 2009;2(3): 98-103. Available from: doi.org/10.1007/s12177-009-9034-6.
14. Kokubun T., Tsuda S., Kunikata H. et al. Characteristic profiles of inflammatory cytokines in the aqueous humor of glaucomatous eyes. Ocul. Immunol. Inflamm. 2017;16: 1. Available from: doi.org/10.1080/09273948.2017.1327605.
15. Tong Y., Zhou Y.L., Zheng Y. et al. Analyzing cytokines as biomarkers to evaluate severity of glaucoma. Int. J. Ophthalmol. 2017;10(6): 925-930. Available from: doi.org/10.18240/ijo.2017.06.15.
16. 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.
17. 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. Available from: doi.org/10.1167/iovs.10-5679.
18. Ikushima H., Miyazono K. Biology of transforming growth factor-β signaling. Current Pharmaceutical Biotechnology. 2011;12(12): 2099–2107. Available from: doi.org/10.2174/138920111798808419.
19. Kajdaniuk D., Marek B., Borgiel-Marek H., Kos-Kudła B. Transforming growth factor β1 (TGFβ1) in physiology and pathology. Endokrynol. Pol. 2013;64(5): 384-396. Available from: doi.org/10.5603/ep.2013.0022.
20. Poniatowski Ł., Wojdasiewicz P., Gasik R., Szukiewicz D. Transforming growth factor Beta family: insight into the role of growth factors in regulation of fracture healing biology and potential clinical applications.Mediators Inflamm. 2015;2015: 137823. Available from: doi.org/10.1155/2015/137823.
21. 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. Вестник офтальмологии. 2010;126(3): 25-29.
22. Braunger B.M., Fuchshofer R., Tamm E.R. The aqueous humor outflow pathways in glaucoma: A unifying concept of disease mechanisms and causative treatment. Eur. J. Pharm Biopharm. 2015;95: 173-181. Available from: doi.org/10.1016/j.ejpb.2015.04.029.
23. Murphy-Ullrich J.E., Downs J.C. The Thrombospondin1-TGF-β Pathway and Glaucoma. J. Ocul. Pharmacol. Ther. 2015;31(7): 371-375. Available from: doi.org/10.1089/jop.2015.0016.
24. Prendes M., Harris A., Wirostko B.M. et al. The role of transforming growth factor β in glaucoma and the therapeutic implications. Br. J. Ophthalmol. 2013;97: 680-686. Available from: doi.org/10.1136/bjophthalmol-2011-301132.
25. Wordinger R.J., Sharma T., Clark A.F. The role of TGF-β2 and bone morphogenetic proteins in the trabecular meshwork and glaucoma. J. Ocul. Pharmacol. Ther. 2014;30(2-3): 154-162. Available from: doi.org/10.1089/jop.2013.0220.
Fyodorov Journal of Ophthalmic Surgery. 2019; : 13-17
Features of the content of transforming growth factors – beta 1,2,3 (TGF-β1, TGF-β2, TGF-β3) in intraocular fluid in primary open-angle glaucoma
https://doi.org/10.25276/0235-4160-2019-2-13-17Abstract
Purpose. To study transforming growth factors – beta 1,2,3 (TGF-β1, TGF-β2, TGF-β3) in intraocular aqueous humor (AH) of patients with the advanced stage of primary open angle glaucoma (POAG).
Material and methods. The study included an examination of 56 patients with advanced stage of POAG which comprised the main group. The diagnosis of POAG was confirmed based on ophthalmological examination. The control group consisted of 30 patients with uncomplicated cataract. TGF-β isoforms concentrations were detected by flow fluorimetry using Bio-Plex Pro™ TGF-β 3-plex Assay and double-beam laser analyzer Bio-Plex 200, Bio-Rad, USA. Three isoforms of TGF-β (TGF-β1, TGF-β2, TGF-β3) were simultaneously detected in AH.
Results. The study revealed a significant increase of TGF-β isoforms concentrations in AH of the advanced POAG compared to AH of the group with uncomplicated cataract: TGF-β1 (3.1 times higher), TGF-β2 (1.4 times) and TGF-β3 (6.9 times). The following direct significant correlations were found: between TGF-β1 and TGF-β2 (r=0.41, p<0.03), between TGF-β1 and TGF-β3 (r=0.83, p<0.004), and between TGF-β2 and TGF-β3 (r=0.35, p<0.04).
Conclusion. We determined a simultaneous increase of concentrations of the studied representatives of super-family transforming growth factors, which have an anti-inflammatory activity, potential to stimulate proliferation, cellular growth, synthesis of proteins of extracellular matrix, etc. These results prove their importance in the POAG pathogenesis.
References
1. Trunov A.N., Bgatova N.P., Eremina A.V. i dr. Novye podkhody k otsenke vyrazhennosti vospalitel'nykh narushenii v patogeneze pervichnoi otkrytougol'noi glaukomy. Allergologiya i immunologiya. 2016;17(2): 107-111.
2. Chernykh V.V., Bgatova N.P., Ermakova O.V. i dr. Mestnyi vospalitel'nyi protsess kak vozmozhnoe proyavlenie narushenii uveolimfaticheskogo ottoka vnutriglaznoi zhidkosti pri glaukome. Ch. 2. Natsional'nyi zhurnal glaukoma. 2018;17(2): 3-11.
3. Carreon T., van der Merwe E., Fellman R.L. et al. Aqueous outflow – A continuum from trabecular meshwork to episcleral veins. Prog. Retin. Eye Res. 2017;57: 108-133. Available from: doi.org/10.1016/j.preteyeres.2016.12.004.
4. 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. Available from: doi.org/10.4172/2155-9570.1000578.
5. Junglas B., Kuespert S., Seleem A.A. et al. Connective tissue growth factor causes glaucoma by modifying the actin cytoskeleton of the trabecular meshwork. Am. J. Pathol. 2012;180(6): 2386-2403. Available from: doi.org/10.1016/j.ajpath.2012.02.030.
6. 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 highsensitivity C-reactive protein in normal-tension glaucoma. J. Ophthalmology. 2016;2016. Available from: http://dx.doi.org/10.1155/2016/2678017.
7. 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.
8. Taurone S., Ripandelli G., Pacella E. et al. 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. Available from: doi.org/10.3892/mmr.2014.2772.
9. Wang K., Read A.T., Sulchek T., Ethier C.R. Trabecular meshwork stiffness in glaucoma. Exp. Eye. Res. 2017;158: 3-12. Available from: doi.org/10.1016/j.exer.2016.07.011.
10. Chernykh V.V., Shvayuk A.P., Gorbenko O.M. i dr. Osobennosti patogeneza nachal'noi i razvitoi stadii pervichnoi otkrytougol'noi glaukomy. Allergologiya i immunologiya. 2006;7(1): 28-31.
11. Chua J., Vania M., Cheung C.M. et al. Expression profile of inflammatory cytokines in aqueous from glaucomatous eyes. Mol. Vis. 2012;18: 431-438.
12. Duvesh R., Puthuran G., Srinivasan K.et al. Multiplex cytokine analysis of aqueous humor from the patients with chronic primary angle closure glaucoma. Curr. Eye Res. 2017;42(12): 1608-1613. Available from: doi.org/10.1080/02713683.2017.1362003.
13. Huang P., Zhang S.S., Zhang C. Erratum: The two sides of cytokine signaling and glaucomatous optic neuropathy. J. Ocul. Biol. Dis. Infor. 2009;2(3): 98-103. Available from: doi.org/10.1007/s12177-009-9034-6.
14. Kokubun T., Tsuda S., Kunikata H. et al. Characteristic profiles of inflammatory cytokines in the aqueous humor of glaucomatous eyes. Ocul. Immunol. Inflamm. 2017;16: 1. Available from: doi.org/10.1080/09273948.2017.1327605.
15. Tong Y., Zhou Y.L., Zheng Y. et al. Analyzing cytokines as biomarkers to evaluate severity of glaucoma. Int. J. Ophthalmol. 2017;10(6): 925-930. Available from: doi.org/10.18240/ijo.2017.06.15.
16. 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.
17. 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. Available from: doi.org/10.1167/iovs.10-5679.
18. Ikushima H., Miyazono K. Biology of transforming growth factor-β signaling. Current Pharmaceutical Biotechnology. 2011;12(12): 2099–2107. Available from: doi.org/10.2174/138920111798808419.
19. Kajdaniuk D., Marek B., Borgiel-Marek H., Kos-Kudła B. Transforming growth factor β1 (TGFβ1) in physiology and pathology. Endokrynol. Pol. 2013;64(5): 384-396. Available from: doi.org/10.5603/ep.2013.0022.
20. Poniatowski Ł., Wojdasiewicz P., Gasik R., Szukiewicz D. Transforming growth factor Beta family: insight into the role of growth factors in regulation of fracture healing biology and potential clinical applications.Mediators Inflamm. 2015;2015: 137823. Available from: doi.org/10.1155/2015/137823.
21. Erichev V.P., Gankovskaya L.V., Koval'chuk L.V., Gankovskaya O.A., Dugina A.E. Izmenenie nekotorykh immunologicheskikh pokazatelei sleznoi zhidkosti pri izbytochnom rubtsevanii posle antiglaukomatoznykh operatsii u patsientov s pervichnoi otkrytougol'noi glaukomoi. Vestnik oftal'mologii. 2010;126(3): 25-29.
22. Braunger B.M., Fuchshofer R., Tamm E.R. The aqueous humor outflow pathways in glaucoma: A unifying concept of disease mechanisms and causative treatment. Eur. J. Pharm Biopharm. 2015;95: 173-181. Available from: doi.org/10.1016/j.ejpb.2015.04.029.
23. Murphy-Ullrich J.E., Downs J.C. The Thrombospondin1-TGF-β Pathway and Glaucoma. J. Ocul. Pharmacol. Ther. 2015;31(7): 371-375. Available from: doi.org/10.1089/jop.2015.0016.
24. Prendes M., Harris A., Wirostko B.M. et al. The role of transforming growth factor β in glaucoma and the therapeutic implications. Br. J. Ophthalmol. 2013;97: 680-686. Available from: doi.org/10.1136/bjophthalmol-2011-301132.
25. Wordinger R.J., Sharma T., Clark A.F. The role of TGF-β2 and bone morphogenetic proteins in the trabecular meshwork and glaucoma. J. Ocul. Pharmacol. Ther. 2014;30(2-3): 154-162. Available from: doi.org/10.1089/jop.2013.0220.
