Журналов:     Статей:        

Офтальмохирургия. 2015; : 50-54

НАРУШЕНИЯ ЦИТОКИНОВОЙ РЕГУЛЯЦИИ В ПАТОГЕНЕЗЕ ПРОЛИФЕРАТИВНОЙ ДИАБЕТИЧЕСКОЙ РЕТИНОПАТИИ

Черных Д. В., Смирнов Е. В., Горбенко О. М., Шваюк А. П., Обухова О. О., Трунова Л. А., Черных В. В., Трунов А. Н.

https://doi.org/undefined

Аннотация

РЕФЕРАТ

Цель. Изучить содержание трансформирующего фактора роста бета 2 (TGF-β2), фактора роста сосудистого эндотелия (VEGF), фактора пигментного эпителия (PEDF) и ряда цитокинов в стекловидном теле у пациентов с ПДР для оценки активности пролиферативного и иммуновоспалительного процессов.

Материал и методы. Были исследованы образцы стекловидного тела пациентов с пролиферативной диабетической ретинопатией и тракционной отслойкой сетчатки и пациентов с тракционной отслойкой сетчатки без ПДР (контроль). Методом иммуноферментного анализа были определены концентрации TGF- β2, VEGF, PEDF МСР-1 интерлейкинов 4, 6, 8, 10, 17А.

Результаты. В стекловидном теле пациентов с ПДР определяется достоверное повышение концентраций провоспалительных цитокинов ИЛ-17А, ИЛ-8, ИЛ-6, МСР-1, противовоспалительного цитокина ИЛ-4, трансформирующего фактора роста бета 2, фактора роста сосудистого эндотелия, фактора пигментного эпителия и моноцитарного хемотаксического белка-1.

Выводы. Полученные данные свидетельствуют о наличии нарушений цитокиновой регуляции в патогенезе ПДР. Установлено, что в патогенезе ПДР определяется активность местного воспалительного и пролиферативного процессов. Выявленные коррелятивные взаимосвязи свидетельствуют о взаимозависимости этих процессов. Выявленное в исследовании достоверное повышение в стекловидном теле пациентов с ПДР белка MCP-1 позволяет сделать предположение об его участии в механизмах сосудистой пролиферации.

Список литературы

1. Глазные проявления диабета / Под ред. Л.И. Балашевича. – СПб., 2004. – 382 с.

2. Либман Е.С., Шахова Е.В. Слепота и инвалидность вследствие патологии органа зрения в России // Вест. офтальмол. – 2006. – № 1. – С. 35-37.

3. Слепова О.С., Нероев В.В., Илюхин П.А., Сарыгина О.И. Иммунологический контроль при хирургическом лечении больных с пролиферативной диабетической ретинопатией с предварительным интраветриальным введением Луцентиса // Рос. офтальмол. журн. – 2012. – № 1. – С. 69-74.

4. Черных В.В., Варваринский Е.В., Горбенко О.М. и др. Активность местного воспалительного и пролиферативного процесса в патогенезе диабетической ретинопатии // Бюл. СО РАМН. – 2013. – Т. 33, № 5. – С. 60-64.

5. Черных В.В., Лысиков А.Г., Братко В.И., Трунов А.Н. Влияние эфферентных и лимфотропных технологий на течение патологического процесса при диабетической ретинопатии // Офтальмохирургия. – 2008. – № 3. – С. 4-7.

6. Bhavsar A.R. Diabetic retinopathy: the latest in current management // Retina. – 2006. – Vol. 26, № 6. – Р. 71-79.

7. Citirik M., Kabatas E.U., Batman C., Akin K.O., Kabatas N. Vitreous vascular endothelial growth factor concentrations in proliferative diabetic retinopathy versus proliferative vitreoretinopathy // Ophthalmic Res. – 2012. – Vol. 47, № 1. – P. 7-12.

8. Goede V., Brogelli L., Ziche M., Augustin H.G. Induction of inflammatory angiogenesis by monocyte chemoattractant protein-1 // Int. J. Cancer. – 1999. – Vol. 82, № 5. – P. 765-770.

9. Kanellakis P., Ditiatkovski M., Kostolias G., Bobik A. A pro-fibrotic role for interleukin-4 in cardiac pressure overload // Cardiovasc. Res. – 2012. – Vol. 95, № 1. – P. 77-85.

10. Kang M.H., Kim M.K., Lee H.J. et al. Interleukin-17 in various ocular surface inflammatory diseases // J. Korean Med. Sci. – 2011. – Vol. 26, № 7. – P. 938-944.

11. Kollias A.N., Ulbig M.W. Diabetic retinopathy: Early diagnosis and effective treatment // Dtsch. Arztebl. Int. – 2010. – Vol. 107, № 5. – P. 75-83.

12. Kowluru R.A., Zhong Q., Kanwar M. Metabolic memory and diabetic retinopathy: role of inflammatory mediators in retinal pericytes // Exp. Eye Res. – 2010. – Vol. 90, № 5. – P. 617-623.

13. Lim A., Stewart J., Chui T.Y. et al. Prevalence and risk factors of diabetic retinopathy in a multi-racial underserved population // Ophthalmic Epidemiol. – 2008. – Vol. 15, № 6. – P. 402-409.

14. Matsuoka M., Ogata N., Minamino K., Matsumura M. Expression of pigment epithelium-derived factor and vascular endothelial growth factor in fibrovascular membranes from patients with proliferative diabetic retinopathy // Jpn. J. Ophthalmol. – 2006. – Vol. 50, № 2. – P. 116-120.

15. Mohan N., Monickaraj F., Balasubramanyam M., Rema M., Mohan V. Imbalanced levels of angiogenic and angiostatic factors in vitreous, plasma and postmortem retinal tissue of patients with proliferative diabetic retinopathy // J. Diabetes Complications. – 2012. – Vol. 26, № 5. – P. 435-441.

16. Murugeswari P., Shukla D., Rajendran A. et al. Proinflammatory cytokines and angiogenic and anti-angiogenic factors in vitreous of patients with proliferative diabetic retinopathy and eales’ disease // Retina. – 2008. – Vol. 28, № 6. – P. 817-824.

17. Neurath M.F., Finotto S. IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer // Cytokine Growth Factor Rev. – 2011. – Vol. 22, № 2. – P. 83-89.

18. Ogata N., Nishikawa M., Nishimura T., Mitsuma Y., Matsumura M. Unbalanced vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in diabetic retinopathy // Am. J. Ophthalmol. – 2002. – Vol. 134, № 3. – P. 348-353.

19. Pennock S., Kazlauskas A. Vascular endothelial growth factor A competitively inhibits platelet-derived growth factor (PDGF)-dependent activation of PDGF receptor and subsequent signaling events and cellular responses // Mol. Cell Biol. – 2012. – Vol. 32, № 10. – P. 1955-1966.

20. Postlethwaite A.E., Holness M.A., Katai H., Raghow R. Human fibroblasts synthesize elevated levels of extracellular matrix proteins in response to interleukin 4 // J. Clin. Invest. – 1992. – Vol. 90, № 4. – P. 1479-1485.

21. Regan D.P., Aarnio M.C., Davis W.S. et al. Characterization of cytokines associated with Th17 cells in the eyes of horses with recurrent uveitis // Vet. Ophtalmol. – 2012. – Vol. 15, № 3. – P. 145-152.

22. Sadaka A., Giuliari G.P. Proliferative vitreoretinopathy: current and emerging treatments // Clin. Ophthalmol. – 2012. – № 6. – P. 1325-1333.

23. Salcedo R., Ponce M.L., Young H.A. et al. Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression // Blood. – 2000. – Vol. 96, № 1. – P. 34-40.

24. Suzuki Y., Nakazawa M., Suzuki K., Yamazaki H., Miyagawa Y. Expression profiles of cytokines and chemokines in vitreous fluid in diabetic retinopathy and central retinal vein occlusion // Jpn. J. Ophthalmol. – 2011. – Vol. 55, № 3. – P. 256-263.

25. Symeonidis C., Papakonstantinou E., Androudi S. et al. Interleukin-6 and the matrix metalloproteinase response in the vitreous during proliferative vitreoretinopathy // Cytokine. – 2011. – Vol. 54, № 2. – P. 212-217.

26. Wakabayashi Y., Usui Y., Okunuki Y. et al. Correlation of vascular endothelial growth factor with chemokines in the vitreous in diabetic retinopathy // Retina. – 2010. – Vol. 30, № 2. – P. 339-344.

27. Wakabayashi Y., Usui Y., Okunuki Y. et al. Increases of vitreous monocyte chemotactic protein 1 and interleukin 8 levels in patients with concurrent hypertension and diabetic retinopathy // Retina. – 2011. – Vol. 31, № 9. – P. 1951-1957.

28. Wakabayashi Y., Usui Y., Okunuki Y. et al. Intraocular VEGF level as a risk factor for postoperative complications after vitrectomy for proliferative diabetic retinopathy // Invest. Ophthalmol. Vis. Sci. – 2012. – Vol. 53, № 10. – P. 6403-6410.

29. Zorena K., Raczyñska D., Wiśniewski P. Relationship between serum transforming growth factor β 1 concentrations and the duration of type 1 diabetes mellitus in children and adolescents // Mediators Inflamm. – 2013. – Vol. 2013. – P. 849457.

Fyodorov Journal of Ophthalmic Surgery. 2015; : 50-54

VIOLATIONS OF CYTOKINE REGULATION IN THE PATHOGENESIS OF PROLIFERATIVE DIABETIC RETINOPATHY

Chernykh D. V., Smirnov E. V., Gorbenko O. M., Shvayuk A. P., Obuhova O. O., Trunova L. A., Chernykh V. V., Trunov A. N.

https://doi.org/undefined

Abstract

Purpose. To study the content of the transforming growth factorbeta 2 (TGF-β2), vascular endothelial growth factor (VEGF), pigment epithelium factor (PEDF) and several cytokines in the vitreous body in patients with proliferative diabetic retinopathy (PDR), to evaluate an activity of proliferative and immune-inflammatory process.

Material and methods. Vitreous samples of patients with proliferative diabetic retinopathy and retinal detachment traction were examined as well as patients with traction retinal detachment without the PDR (control). Concentration of TGF- β 2, VEGF, PEDF MCP-1, interleukin 4, 6, 8, 10, 17A was determined by the ELISA method.

Results. A reliable increase in the concentrations of pro-inflammatory cytokines IL-17A, IL-8, IL-6, MCP-1, anti-inflammatory cytokine IL-4, transforming growth factor-beta 2, vascular endothelial growth factor, factor of pigment epithelium and monocyte chematacticprotein-1 was detected in the vitreous of PDR patients.

Conclusions. The findings indicate the existence of cytokine regulation violations in the PDR pathogenesis. It was noted that the activity of local inflammatory and proliferative processes was determined in the PDR pathogenesis. The revealed correlative relationships indicate interdependence of these processes. The detected reliable increase of monocyte chemotactic protein-1 in the vitreous of PDR patients, allows to make an assumption about its participation in the mechanisms of vascular proliferation.

References

1. Glaznye proyavleniya diabeta / Pod red. L.I. Balashevicha. – SPb., 2004. – 382 s.

2. Libman E.S., Shakhova E.V. Slepota i invalidnost' vsledstvie patologii organa zreniya v Rossii // Vest. oftal'mol. – 2006. – № 1. – S. 35-37.

3. Slepova O.S., Neroev V.V., Ilyukhin P.A., Sarygina O.I. Immunologicheskii kontrol' pri khirurgicheskom lechenii bol'nykh s proliferativnoi diabeticheskoi retinopatiei s predvaritel'nym intravetrial'nym vvedeniem Lutsentisa // Ros. oftal'mol. zhurn. – 2012. – № 1. – S. 69-74.

4. Chernykh V.V., Varvarinskii E.V., Gorbenko O.M. i dr. Aktivnost' mestnogo vospalitel'nogo i proliferativnogo protsessa v patogeneze diabeticheskoi retinopatii // Byul. SO RAMN. – 2013. – T. 33, № 5. – S. 60-64.

5. Chernykh V.V., Lysikov A.G., Bratko V.I., Trunov A.N. Vliyanie efferentnykh i limfotropnykh tekhnologii na techenie patologicheskogo protsessa pri diabeticheskoi retinopatii // Oftal'mokhirurgiya. – 2008. – № 3. – S. 4-7.

6. Bhavsar A.R. Diabetic retinopathy: the latest in current management // Retina. – 2006. – Vol. 26, № 6. – R. 71-79.

7. Citirik M., Kabatas E.U., Batman C., Akin K.O., Kabatas N. Vitreous vascular endothelial growth factor concentrations in proliferative diabetic retinopathy versus proliferative vitreoretinopathy // Ophthalmic Res. – 2012. – Vol. 47, № 1. – P. 7-12.

8. Goede V., Brogelli L., Ziche M., Augustin H.G. Induction of inflammatory angiogenesis by monocyte chemoattractant protein-1 // Int. J. Cancer. – 1999. – Vol. 82, № 5. – P. 765-770.

9. Kanellakis P., Ditiatkovski M., Kostolias G., Bobik A. A pro-fibrotic role for interleukin-4 in cardiac pressure overload // Cardiovasc. Res. – 2012. – Vol. 95, № 1. – P. 77-85.

10. Kang M.H., Kim M.K., Lee H.J. et al. Interleukin-17 in various ocular surface inflammatory diseases // J. Korean Med. Sci. – 2011. – Vol. 26, № 7. – P. 938-944.

11. Kollias A.N., Ulbig M.W. Diabetic retinopathy: Early diagnosis and effective treatment // Dtsch. Arztebl. Int. – 2010. – Vol. 107, № 5. – P. 75-83.

12. Kowluru R.A., Zhong Q., Kanwar M. Metabolic memory and diabetic retinopathy: role of inflammatory mediators in retinal pericytes // Exp. Eye Res. – 2010. – Vol. 90, № 5. – P. 617-623.

13. Lim A., Stewart J., Chui T.Y. et al. Prevalence and risk factors of diabetic retinopathy in a multi-racial underserved population // Ophthalmic Epidemiol. – 2008. – Vol. 15, № 6. – P. 402-409.

14. Matsuoka M., Ogata N., Minamino K., Matsumura M. Expression of pigment epithelium-derived factor and vascular endothelial growth factor in fibrovascular membranes from patients with proliferative diabetic retinopathy // Jpn. J. Ophthalmol. – 2006. – Vol. 50, № 2. – P. 116-120.

15. Mohan N., Monickaraj F., Balasubramanyam M., Rema M., Mohan V. Imbalanced levels of angiogenic and angiostatic factors in vitreous, plasma and postmortem retinal tissue of patients with proliferative diabetic retinopathy // J. Diabetes Complications. – 2012. – Vol. 26, № 5. – P. 435-441.

16. Murugeswari P., Shukla D., Rajendran A. et al. Proinflammatory cytokines and angiogenic and anti-angiogenic factors in vitreous of patients with proliferative diabetic retinopathy and eales’ disease // Retina. – 2008. – Vol. 28, № 6. – P. 817-824.

17. Neurath M.F., Finotto S. IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer // Cytokine Growth Factor Rev. – 2011. – Vol. 22, № 2. – P. 83-89.

18. Ogata N., Nishikawa M., Nishimura T., Mitsuma Y., Matsumura M. Unbalanced vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in diabetic retinopathy // Am. J. Ophthalmol. – 2002. – Vol. 134, № 3. – P. 348-353.

19. Pennock S., Kazlauskas A. Vascular endothelial growth factor A competitively inhibits platelet-derived growth factor (PDGF)-dependent activation of PDGF receptor and subsequent signaling events and cellular responses // Mol. Cell Biol. – 2012. – Vol. 32, № 10. – P. 1955-1966.

20. Postlethwaite A.E., Holness M.A., Katai H., Raghow R. Human fibroblasts synthesize elevated levels of extracellular matrix proteins in response to interleukin 4 // J. Clin. Invest. – 1992. – Vol. 90, № 4. – P. 1479-1485.

21. Regan D.P., Aarnio M.C., Davis W.S. et al. Characterization of cytokines associated with Th17 cells in the eyes of horses with recurrent uveitis // Vet. Ophtalmol. – 2012. – Vol. 15, № 3. – P. 145-152.

22. Sadaka A., Giuliari G.P. Proliferative vitreoretinopathy: current and emerging treatments // Clin. Ophthalmol. – 2012. – № 6. – P. 1325-1333.

23. Salcedo R., Ponce M.L., Young H.A. et al. Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression // Blood. – 2000. – Vol. 96, № 1. – P. 34-40.

24. Suzuki Y., Nakazawa M., Suzuki K., Yamazaki H., Miyagawa Y. Expression profiles of cytokines and chemokines in vitreous fluid in diabetic retinopathy and central retinal vein occlusion // Jpn. J. Ophthalmol. – 2011. – Vol. 55, № 3. – P. 256-263.

25. Symeonidis C., Papakonstantinou E., Androudi S. et al. Interleukin-6 and the matrix metalloproteinase response in the vitreous during proliferative vitreoretinopathy // Cytokine. – 2011. – Vol. 54, № 2. – P. 212-217.

26. Wakabayashi Y., Usui Y., Okunuki Y. et al. Correlation of vascular endothelial growth factor with chemokines in the vitreous in diabetic retinopathy // Retina. – 2010. – Vol. 30, № 2. – P. 339-344.

27. Wakabayashi Y., Usui Y., Okunuki Y. et al. Increases of vitreous monocyte chemotactic protein 1 and interleukin 8 levels in patients with concurrent hypertension and diabetic retinopathy // Retina. – 2011. – Vol. 31, № 9. – P. 1951-1957.

28. Wakabayashi Y., Usui Y., Okunuki Y. et al. Intraocular VEGF level as a risk factor for postoperative complications after vitrectomy for proliferative diabetic retinopathy // Invest. Ophthalmol. Vis. Sci. – 2012. – Vol. 53, № 10. – P. 6403-6410.

29. Zorena K., Raczyñska D., Wiśniewski P. Relationship between serum transforming growth factor β 1 concentrations and the duration of type 1 diabetes mellitus in children and adolescents // Mediators Inflamm. – 2013. – Vol. 2013. – P. 849457.