Офтальмохирургия. 2015; : 36-42
Экспрессия ростовых, трофических и провоспалительных факторов в эпиретинальных мембранах пациентов с тяжелой формой пролиферативной витреоретинопатии
https://doi.org/undefinedАннотация
Пролиферативная витреоретинопатия (ПВР) возникает вследствие воспалительных процессов в глазу, осложняющих течение регматогенной отслойки сетчатки. Пролиферацию клеток на поверхности сетчатки и образование эпиретинальных мембран стимулируют ростовые факторы и медиаторы воспаления. Циклооксигеназы (ЦОГ) катализируют продукцию простагландинов из арахидоновой кислоты, что является одним из механизмов инициации и поддержания воспалительной реакции. Фактор роста нервов (NGF) и мозговой нейротрофический фактор (BDNF) обеспечивают жизнеспособность нейронов и глиальных клеток сетчатки. Эндотелиальный фактор роста сосудов (VEGF) обладает ангиогенными, нейропротекторными, антиапоптотическими эффектами на сетчатку.
Цель. Изучить уровень экспрессии ЦОГ-1 и ЦОГ-2, нейротрифинов BDNF и NGF, VEGF в эпиретинальных мембранах пациентов с тяжелой формой пролиферативной витреоретинопатии.
Материал и методы. Методом полимеразной цепной реакции (ПЦР) в эпиретинальных мембранах, забранных у 11 пациентов, страдающих ПВР, во время хирургического вмешательства на сетчатке определяли экспрессию мРНК ЦОГ первого и второго типов, NGF, BDNF и VEGF.
Результаты. В мембранах была выявлена экспрессия мРНК ЦОГ-1 и ЦОГ-2, VEGF и BDNF. NGF обнаружили в трех образцах. Выявили прямую зависимость количества мРНК ЦОГ-1,VEGF и BDNF.
Обсуждение. Полученные данные позволяют сделать вывод о том, что наличие мембраны, образующейся при ПВР, способствует поддержанию воспаления в глазу и стимулирует собственный рост. С одной стороны, мембраны выполняют нейропротекторную функцию, секретируя факторы роста, что сохраняет жизнеспособность ганглионарных клеток сетчатки, находящихся непосредственно под фиброзированной тканью, с другой – продукция этих факторов обеспечивает жизнеспособность, рост и развитие клеток самой мембраны.
Заключение. В работе впервые выявлено, что в мембранах, образующихся при отслойке сетчатки, осложненной ПВР, экспрессируются ЦОГ-1, ЦОГ-2, BDNF и VEGF. Синтез же NGF наблюдается в 30% случаев. Показано, что в эпиретинальных мембранах, образующихся при ПВР, наблюдается взаимосвязь между экспрессией ЦОГ-1, VEGF и BDNF.
Список литературы
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29. Rouzer C.A., Marnett L.J. Cyclooxygenases: structural and functional insights // J. Lipid. Res. – 2009. – Vol. 50 – P. 29-34.
30. Saint-Geniez M., Maharaj A., Walshe T.E. et al. Endogenous VEGF is required for visual function: Evidence for a survival role on Muller cells and photoreceptors // PLoS One. – 2008. – Vol. 3, № 11. – P. 1-13.
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32. The Retina Society Terminology Committee. The classification of retinal detachment with proliferative vitreoretinopathy // Ophthalmology. – 1983. – Vol. 90. – P. 121-125.
33. Tonchev A.B. Brain ischemia, neurogenesis, and neurotrophic receptor expression in primates // Arch. Ital. Biol. – 2011. – Vol. 149, № 2. – P. 225-231.
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Fyodorov Journal of Ophthalmic Surgery. 2015; : 36-42
Expression of growth, trophic and inflammation factors in epiretinal membranes in patients with severe proliferative vitreoretinopathy
https://doi.org/undefinedAbstract
Proliferative vitreoretinopathy (PVR) – an ocular pathology is caused by an eye inflammation, complicating the course of rhegmatogenous retinal detachment. Cell proliferation on the surface of the retina and epiretinal membrane formation are stimulated by growth factors and inflammatory mediators. Cyclooxygenase (COX) catalyzes the production of prostaglandins from arachidonic acid, that is one of the mechanisms of initiation and maintenance of the inflammatory reaction. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) ensure the viability of neurons and glial cells in the retina. Vascular endothelial growth factor (VEGF) has angiogenic, neuroprotective, anti-apoptotic effects on the retina.
Purpose. To examine the expression level of COX-1 and COX-2, neurotrophins BDNF and NGF, VEGF in epiretinal membranes from patients with a severe proliferative vitreoretinopathy.
Material and methods. The mRNA expression of COX (of the first and second types), NGF, BDNF and VEGF were determined by PCR in epiretinal membranes, taken from 11 patients suffering from the PVR during surgery on the retina.
Results. Membranes were detected to express mRNA of COX-1 and COX-2, VEGF and BDNF. NGF was found in three samples. We revealed a direct dependence of the amount of mRNA of COX-1, VEGF and BDNF.
Discussion. These data suggest that the presence of membrane, formed under the PVR condition, promotes maintenance of inflammation in the eye and stimulates its own growth. On one side, the membrane performs neuroprotective function by secreting growth factors that preserve the viability of retinal ganglion cells which are situated directly under the fibrous tissue, on the other – the production of these factors ensures the viability, growth and development of membrane cells.
Conclusion. For the first time it is found that COX-1, COX-2, BDNF and VEGF are expressed in the membranes, formed as a result of rhegmatogenous retinal detachment complicated by PVR. NGF synthesis is observed in 30% of cases. Correlations in expression of COX-1, VEGF and BDNF are observed in epiretinal membranes formed in the course of PVR.
References
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4. Alon T., Hemo I., Itin A. et al. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity // Nat. Med. – 1995. – Vol. 1, № 10. – P. 1024-1028.
5. Binder D.K., Scharfman H.E. Brainderived Neurotrophic Factor // Growth Factors. – 2004. – Vol. 22, № 3. – P. 123-131.
6. Böcker-Meffert S., Rosenstiel P., Röhl C. et al. Erythropoietin and VEGF promote neural outgrowth from retinal explants in postnatal rats // Invest. Ophthalmol. Vis. Sci. – 2002. – Vol. 43, № 6. – P. 2021-2026.
7. Bryant C.E., Appleton I., Mitchell J.A. Vascular endothelial growth factor upregulates constitutive cyclooxygenase 1 in primary bovine and human endothelial cells // Life Sci. – 1998. – Vol. 62, № 24. –P. 2195-2201.
8. Colafrancesco V., Coassin M., Rossi S., Aloe L. Effect of eye NGF administration on two animal models of retinal ganglion cells degeneration // Ann. Ist. Super Sanita. – 2011. – Vol. 47, № 3. – P. 284-289.
9. Dolle J., Rezvan A., Allen F. et al. Nerve Growth Factor-Induced Migration of Endothelial Cells // J. Pharmacol. Exp. Ther. – 2005. – Vol. 315, № 3. – P. 1220- 1227.
10. Donovan M.J., Lin M., Wiegn P. et al. Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization // Development. – 2000. – Vol. 127, № 21. – P. 4531-4540.
11. Forstreuter F., Lucius R., Mentlein R. Vascular endothelial growth factor induces chemotaxis and proliferation of microglial cells // J. Neuroimmunol. – 2002. – Vol. 132, № 1-2. – P. 93-98.
12. Ghazi-Nouri S., Ellis J., Moss S. et al. Expression and localisation of BDNF, NT4 and TrkB in proliferative vitreoretinopathy // Exp. Eye Res. – 2008. – Vol. 86, № 5. – P. 819-827.
13. Harada C., Guo X., Namekata K. et al. Glia- and neuron-specific functions of TrkB signalling during retinal degeneration and regeneration // Nat. Commun. Nature Publishing Group. – 2011. – Vol. 2. – P. 189.
14. Kase S., Saito W., Ohno S., Ishida S. Cyclo-oxygenase-2 expression in human idiopathic epiretinal membrane // Retina. – 2010. – Vol. 30, № 5. – P. 719-723.
15. Kermani P., Rafii D., Jin D. et al. Neurotrophins promote revascularization by local recruitment of TrkB + endothelial cells and systemic mobilization of hematopoietic progenitors // J. Clin. Invest. – 2005. – Vol. 115, № 3. – P. 653-663.
16. Kim I., Ryan A., Rohan R. et al. Constitutive Expression of VEGF, VEGFR-1, and VEGFR-2 in Normal Eyes // Invest. Ophthalmol. Vis. Sci. – 1999. – Vol. 40. – P. 2115-2121.
17. Langenbach R., Morham S., Tiano H. et al. Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration // Cell. – 1995. – Vol. 83, № 3. – P. 483-492.
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19. Lewis G.P., Linberg K.A., Geller S.F. et al. Effects of the neurotrophin brain-derived neurotrophic factor in an experimental model of retinal detachment // Investig. Ophthalmol. Vis. Sci. – 1999. – Vol. 40, № 7. – P. 1530-1544.
20. Liu X., Wang D. Liu Y. et al. Neuronaldriven angiogenesis: role of NGF in retinal neovascularization in an oxygen-induced retinopathy model // Invest. Ophthalmol. Vis. Sci. – 2010. – Vol. 51, № 7. – P. 3749-3757.
21. Louissaint A., Rao S., Leventhal C., Goldman S. A. Coordinated interaction of neurogenesis and angiogenesis in the adult songbird brain // Neuron. – 2002. – Vol. 34, № 6. – P. 945-960.
22. Maloney S.C., Fernandes B.F., Castiglione E. et al. Expression of cyclooxygenase- 2 in choroidal neovascular membranes from age-related macular degeneration patients // Retina. – 2009. – Vol. 29, № 2. – P. 176-180.
23. Mansour-Robaey S., Clarke D.B., Wang Y.C. et al. Effects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells // Proc. Natl. Acad. Sci. U.S.A. – 1994. – Vol. 91, № 5. – P. 1632-1636.
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25. Nico B., Mangieri D., Benagiano V. et al. Nerve growth factor as an angiogenic factor // Microvasc. Res. – 2008. – Vol. 75, № 2. – P. 135-141.
26. Pagès G., Pouysségur J. Transcriptional regulation of the Vascular Endothelial Growth Factor gene – A concert of activating factors // Cardiovasc. Res. – 2005. – Vol. 65, № 3. – P. 564-573.
27. Pierce E.A., Avery R.L., Foley E. et al. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization // Proc. Natl. Acad. Sci. U.S.A. – 1995. – Vol. 92, № 3. – P. 905-909.
28. Radi Z.A., Render J.A. The pathophysiologic role of cyclo-oxygenases in the eye // J. Ocul. Pharmacol. Ther. – 2008. – Vol. 24, № 2. – P. 141-151.
29. Rouzer C.A., Marnett L.J. Cyclooxygenases: structural and functional insights // J. Lipid. Res. – 2009. – Vol. 50 – P. 29-34.
30. Saint-Geniez M., Maharaj A., Walshe T.E. et al. Endogenous VEGF is required for visual function: Evidence for a survival role on Muller cells and photoreceptors // PLoS One. – 2008. – Vol. 3, № 11. – P. 1-13.
31. Sivilia S., Giuliani A., Fernández M. et al. Intravitreal NGF administration counteracts retina degeneration after permanent carotid artery occlusion in rat // BMC Neurosci. – 2009. – Vol. 10, № 52. – P. 1-14.
32. The Retina Society Terminology Committee. The classification of retinal detachment with proliferative vitreoretinopathy // Ophthalmology. – 1983. – Vol. 90. – P. 121-125.
33. Tonchev A.B. Brain ischemia, neurogenesis, and neurotrophic receptor expression in primates // Arch. Ital. Biol. – 2011. – Vol. 149, № 2. – P. 225-231.
34. Wilkinson-Berka J. Vasoactive factors and diabetic retinopathy: vascular endothelial growth factor, cycoloxygenase-2 and nitric oxide // Curr. Pharm. Des. – 2004. – Vol. 10, № 27. – P. 3331-3348.
