mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-PAL-2002mimmun-2002Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESИзвестные и малоизученные гемопоэтические и вазоактивные факторы роста при капиллярной гемангиоме сетчаткиProven and less studied hematopoietic and vasoactive growth factors in retinal capillary hemangiomaНероевВ. В.NeroevV. V.

Нероев Владимир Владимирович – доктор медицинских наук, профессор, академик РАН, директор

Москва

Neroev Vladimir V., PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Director

Moscow

kanc@igb.ruБалацкаяН. В.BalatskayaN. V.

 Балацкая Наталья Владимировна – кандидат биологических наук, ведущий научный сотрудник, начальник отдела иммунологии и вирусологии

Москва

Balatskaya Natalya V., PhD (Biology), Leading Research Associate, Head, Department of Immunology and Virology

Moscow

balnat07@rambler.ruНовиковаА. Ю.NovikovaA. Yu.

Новикова Анна Юрьевна – аспирант отдела патологии сетчатки и зрительного нерва

105062, Москва, ул. Садовая-Черногрязская, 14/19

Novikova Anna Yu., Postgraduate Student, Department of Retinal and Optic Nerve Pathology

105062, Moscow, SadovayaChernogryazskaya str., 14/19

ayukolesnikova@gmail.comРябинаМ. В.RyabinaM. V.

Рябина Марина Владимировна – кандидат медицинских наук, старший научный сотрудник отдела патологии сетчатки и зрительного нерва

Москва

Ryabina Marina V., PhD (Medicine), Senior Research Associate, Department of Retinal and Optic Nerve Pathology

Moscow

mryabina@yandex.ruИлюхинП. А.IlyukhinP. A.

Илюхин Павел Андреевич – кандидат медицинских наук, научный сотрудник отдела патологии сетчатки и зрительного нерва

Москва

Ilyukhin Pavel A., PhD (Medicine), Research Associate, Department of Retinal and Optic Nerve Pathology

Moscow

paulilukhin@gmail.comФГБУ «Национальный медицинский исследовательский центр глазных болезней имени Гельмгольца» Министерства здравоохранения РФРоссияHelmholtz National Medical Research Center of Eye DiseasesRussian Federation202027112020225943956Copyright © Нероев В.В., Балацкая Н.В., Новикова А.Ю., Рябина М.В., Илюхин П.А., 20202020Нероев В.В., Балацкая Н.В., Новикова А.Ю., Рябина М.В., Илюхин П.А.Neroev V.V., Balatskaya N.V., Novikova A.Y., Ryabina M.V., Ilyukhin P.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2002

В настоящее время патогенез развития капиллярной гемангиомы сетчатки изучен недостаточно. В связи с этим исследование уровней цитокинов в биологических жидкостях представляется весьма актуальным с целью расширения знаний о механизмах развития заболевания и поиска таргетной терапии. В представленном исследовании изучено содержание в сыворотке крови, слезной жидкости и стекловидном теле гемопоэтических и вазоактивных факторов роста у пациентов с капиллярной гемангиомой сетчатки. Всего обследовано 26 пациентов с ангиоматозом сетчатки. В качестве контроля использовали пробы сыворотки крови (n = 23) и слезной жидкости (n = 10) практически здоровых людей в возрасте от 22 до 46 (27,4±1,4 года) лет. Для сравнительной оценки концентраций цитокинов в стекловидном теле пациентов с капиллярной гемангиомой сетчатки использовали образцы стекловидного тела 6 пациентов (средний возраст 33±4,7 года; от 21 до 49 лет) с регматогенной отслойкой сетчатки. Концентрацию цитокинов в пробах определяли методом мультиплексного анализа на платформе хMAP в программе LuminexxPONENT 3.1, с помощью наборов ProcartaPlex (eBioscience, Австрия). В результате проведенной работы получена подробная характеристика вазоактивных факторов при капиллярной гемангиоме сетчатки. Выявлены нарушения в хемокиновой регуляции. В сыворотке крови было выявлено достоверное увеличение концентраций 3 вазоактивных факторов – PDGF-BB, HGF и PIGF-1, при снижении хемокинов – МСР-1, MIP-1α и MIP-1β. Частота выявления PIGF-1 и MIP-1α также достоверно отличалась от группы контроля. SCF достоверно чаще определялся у пациентов с ангиоматозом сетчатки только на системном уровне. Показаны корреляционные связи между показателями PDGF-BB и PIGF-1, а также PIGF-1 и MIP-1β. В слезной жидкости показано достоверное увеличение концентраций VEGF-A, HGF, VEGF-D, а также MCP-1. Отмечена инверсия концентраций PDGF-BB в сыворотке крови и слезной жидкости. Анализ внутриглазных уровней цитокинов выявил достоверное увеличение концентраций VEGF-A и HGF, при выраженном снижении MIP-1α и MIP-1β. Фактор роста PDGF-BB в 100% случаев определялся только в стекловидном теле пациентов с ангиоматозом сетчатки. С учетом выявленных характерных сдвигов интраокулярной продукции HGF/SF при капиллярной гемангиоме сетчатки, представляется актуальным поиск способов его ингибирования, что может стать основой новой терапевтической стратегии в лечении ангиоматоза сетчатки.

Pathogenesis of retinal capillary hemangioma has not been sufficiently studied at the present time. Therefore, the study of cytokine levels in biological fluids seems to be very relevant in order to increase knowledge about the mechanisms of the disease development and searching for targeted therapies. The content of hematopoietic and vasoactive growth factors in blood serum, lacrimal fluid, and vitreous body was studied in patients with retinal capillary hemangioma. A total of 26 patients with retinal angiomatosis were examined. The samples of blood serum (n = 23) and lacrimal fluid (n = 10) from practically healthy people aged 22 to 46 (27.4±1.4 years) were used as a control. To perform comparative assessment of cytokine concentrations in the vitreous body of patients with retinal capillary hemangioma, were used samples of the vitreous body from 6 patients (average age 33±4.7 years; from 21 to 49 years) with rhegmatogenous retinal detachment. To measure the cytokine concentrations, we applied multiplex analysis technique using the xMAP platform with LuminexxPONENT 3.1 program and ProcartaPlex sets (eBioscience, Austria). A detailed characteristic of vasoactive factors in capillary retinal hemangioma was obtained as a result of this work. Some disorders in chemokine regulation were identified. There was a significant increase in serum concentrations of three vasoactive factors, i.e., PDGF-BB, HGF, and PIGF-1, with a decrease in chemokines (MCP-1, MIP-1α, and MIP-1β). The frequencies of PIGF-1 and MIP-1α detection also significantly differed from the control group. SCF was significantly more often determined in patients with retinal angiomatosis only at the systemic level. Correlations between PDGF-BB and PIGF-1, as well as PIGF-1 and MIP-1β were shown. A significant increase in VEGF-A, HGF, VEGF-D, as well as MCP-1 concentrations was shown in the lacrimal fluid. The inversion of PDGF-BB concentrations in serum and lacrimal fluid was noted. Analysis of intraocular cytokine levels revealed a significant increase in VEGF-A and HGF concentrations, with marked decrease in MIP-1α and MIP-1β. PDGF-BB in 100% of cases was determined only in vitreous body of patients with retinal angiomatosis. With respect to the revealed characteristic shifts of HGF/SF intraocular production in retinal capillary hemangioma, it seems relevant to search ways for its inhibition, thus providing potential basis for a new therapeutic strategy in treatment of retinal angiomatosis.

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