vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ16.200vavilov-859Research ArticleСистемная биология и моделированиеSystems biology and simulationsМолекулярно-генетические механизмы взаимодействия процессов ответа клетки на механический стресс и нейронального апоптоза при первичной открытоугольной глаукомеMolecular-genetic mechanisms of the interaction between processes of cell response to mechanical stress and neuronal apoptosis in primary open-angle glaucomaСайкО. В.SaikO. V.

Новосибирск, Россия

Novosibirsk, Russia

saik@bionet.nsc.ruКоноваловаН. А.KonovalovaN. A.

Тюмень, Россия

Tyumen, Russia

ДеменковП. С.DemenkovP. S.

Новосибирск, Россия

Novosibirsk, Russia

ИванисенкоН. В.IvanisenkoN. V.

Новосибирск, Россия

Novosibirsk, Russia

ИванисенкоТ. В.IvanisenkoT. V.

Новосибирск, Россия

Novosibirsk, Russia

ИванощукД. Е.IvanoshchukD. E.

Новосибирск, Россия

Novosibirsk, Russia

КоноваловаО. С.KonovalovaO. S.

Тюмень, Россия

Tyumen, Russia

ПодколоднаяО. А.PodkolodnayaO. A.

Новосибирск, Россия

Novosibirsk, Russia

ЛаврикИ. Н.LavrikI. N.

Новосибирск, Россия

Магдебург, Германия

Novosibirsk, Russia

Magdeburg, Germany

КолчановН. А.KolchanovN. A.

Новосибирск, Россия

Novosibirsk, Russia

ИванисенкоВ. А.IvanisenkoV. A.

Новосибирск, Россия

Novosibirsk, Russia

Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук» Федеральное государственное бюджетное образовательное учреждение высшего образования «Тюменский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияInstitute of Cytology and Genetics SB RASRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Тюменский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияTyumen State Medical UniversityRussian FederationФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»РоссияInstitute of Cytology and Genetics SB RASRussian FederationФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук»РоссияInstitute of Cytology and Genetics SB RAS Novosibirsk State UniversityRussian FederationФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук» Федеральное государственное автономное образовательное учреждение высшего образования «Новосибирский национальный исследовательский государственный университет»РоссияInstitute of Cytology and Genetics SB RASRussian FederationФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук» Магдебургский университет имени Отто фон ГуерикеРоссияInstitute of Cytology and Genetics SB RAS Institute of Experimental Internal Medicine, Otto von Guericke UniversityRussian Federation201602022017206840847Copyright © Сайк О.В., Коновалова Н.А., Деменков П.С., Иванисенко Н.В., Иванисенко Т.В., Иванощук Д.Е., Коновалова О.С., Подколодная О.А., Лаврик И.Н., Колчанов Н.А., Иванисенко В.А., 20172017Сайк О.В., Коновалова Н.А., Деменков П.С., Иванисенко Н.В., Иванисенко Т.В., Иванощук Д.Е., Коновалова О.С., Подколодная О.А., Лаврик И.Н., Колчанов Н.А., Иванисенко В.А.Saik O.V., Konovalova N.A., Demenkov P.S., Ivanisenko N.V., Ivanisenko T.V., Ivanoshchuk D.E., Konovalova O.S., Podkolodnaya O.A., Lavrik I.N., Kolchanov N.A., Ivanisenko V.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/859

Глаукома – хроническое, прогрессирующее заболевание, которым страдают более 60 млн человек в мире. Первичная открытоугольная глаукома (ПОУГ) занимает одно из первых мест по распространенности среди различных форм глаукомы. Например, в 2011 г. эта форма заболевания наблюдалась более чем у 2.7 млн человек в США. В настоящее время ПОУГ является основной причиной необратимой потери зрения. У больных с открытоугольной глаукомой риск слепоты достигает 27 %, даже несмотря на проводимое лечение. Известно, что гибель клеток зрительного нерва может быть спровоцирована механическим стрессом, вызванным повышенным внутриглазным давлением, наблюдающимся при ПОУГ, индуцирующим нейрональный апоптоз. В настоящее время существует огромное количество научных публикаций, описывающих белки и гены, которые участвуют в патогенезе ПОУГ, в том числе в нейрональном апоптозе и клеточном ответе на механический стресс. Тем не менее молекулярно-генетические механизмы, лежащие в основе патофизиологии ПОУГ, до сих пор плохо изучены. Реконструкция ассоциативных генных сетей, описывающих функциональные взаимодействия между этими генами/ белками, включая биохимические реакции, регуляторные взаимодействия, события транспорта и т. д., требует использования методов автоматизированного извлечения знаний из текстов научных публикаций. В работе проанализированы ассоциативные сети, описывающие молекулярно-генетические взаимодействия между белками и генами, вовлеченными в ответ клетки на механический стресс (ОКМС), нейрональный апоптоз и патогенез ПОУГ. Показано, что гены, ассоциированные с ПОУГ, статистически значимо чаще, чем ожидалось по случайным причинам, представлены среди генов, участвующих во взаимодействии между ОКМС и нейрональным апоптозом, что может быть важным фактором, влияющим на гибель ганглиозных ретинальных клеток при ПОУГ.

Glaucoma is a chronic and progressive disease, which affects more than 60 million people worldwide. Primary open-angle glaucoma (POAG) is one of the most common forms of glaucoma. For example, about 2.71 million people in the USA had primary open-angle glaucoma in 2011. Currently POAG is a major cause of irreversible vision loss. In patients with treated open-angle glaucoma the risk of blindness reached to be about 27 %. It is known that the death of optic nerve cells can be triggered by mechanical stress caused by increased intraocular pressure, which induces neuronal apoptosis and is observed in patients with POAG. Currently, there is a large number of scientific publications describing proteins and genes involved in the pathogenesis of POAG, including neuronal apoptosis and the cell response to mechanical stress. However, the molecular- genetic mechanisms underlying the pathophysiology of POAG are still poorly understood. Reconstruction of associative networks describing the functional interactions between these genes/proteins, including biochemical reactions, regulatory interactions, transport, etc., requires the use of methods of automated knowledge extraction from texts of scientific publications. The aim of the work was the analysis of associative networks, describing the molecular-genetic interactions between proteins and genes involved in cell response to mechanical stress (CRMS), neuronal apoptosis and pathogenesis of POAG using ANDSystem, our previous development for automated text analysis. It was shown that genes associated with POAG are statistically significantly more often represented among the genes involved in the interactions between CRMS and neuronal apoptosis than it was expected by random reasons, which can be an explanation for the effect of POAG leading to the retinal ganglion cell death.

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The authors declare that there are no conflicts of interest present.