mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-SOC-2351mimmun-2351Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESСкрининг цитокинов в сыворотке крови и слезной жидкости при влажной и атрофической формах возрастной макулярной дегенерацииScreening of cytokines in blood serum and lacrimal liquid in wet and atrophic forms of age-related macular degenerationhttps://orcid.org/0000-0002-8480-0894НероевВ. В.NeroevV. V.

Д.м.н., профессор, академик РАН, начальник отдела патологии сетчатки и зрительного нерва, директор

Москва

PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Head, Department of Retinal and Optic Nerve Pathology, Director

Moscow

secr@igb.ruhttps://orcid.org/0000-0001-8007-6643БалацкаяН. В.BalatskayaN. V.

К.б.н., ведущий научный сотрудник, начальник отдела иммунологии и вирусологии

Москва

PhD (Biology), Leading Research Associate, Head, Department of Immunology and Virology

Moscow

balnat07@rambler.ruhttps://orcid.org/0000-0003-1038-2746НероеваН. В.NeroevaN. V.

К.м.н., врач-офтальмолог отдела патологии сетчатки и зрительного нерва

Москва

PhD (Medicine), Clinical Ophthalmologist, Department of Retinal and Optic Nerve Pathology

Moscow

nneroeva@gmail.comhttps://orcid.org/0000-0003-3091-5191КармоковаА. Г.KarmokovaA. G.

Аспирант отдела патологии сетчатки и зрительного нерва

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

Тел.: 8 (963) 669-54-91

Postgraduate Student, Department of Retinal and Optic Nerve Pathology

105062, Moscow, Sadovaya-Chernogryazskaya str. 14/19

Phone: 7 (963) 669-54-91

asyakarma17@gmail.comРябинаМ. В.RyabinaM. V.

К.м.н., врач-офтальмолог, старший научный сотрудник отдела патологии сетчатки и зрительного нерва

Москва

PhD (Medicine), Clinical Ophthalmologist, Senior Research Associate, Department of Retinal and Optic Nerve Pathology

Moscow

mryabina@yandex.ruhttps://orcid.org/0000-0002-1005-5633КуликоваИ. Г.KulikovaI. G.

Старший научный сотрудник отдела отдела иммунологии и вирусологии

Москва

Senior Research Associate, Department of Immunology and Virology

Moscow

ig-kulikova@yandex.ruФГБУ «Национальный медицинский исследовательский центр глазных болезней имени Гельмгольца» Министерства здравоохранения РФРоссияHelmholtz National Medical Research Center of Eye DiseasesRussian FederationФГБУ «Национальный медицинский исследовательский центр глазных болезней имени Гельмгольца» Министерства здравоохранения РФРоссияHelmholtz National Medical Research Center of Eye DiseaseRussian Federation202210032022241157170Copyright © Нероев В.В., Балацкая Н.В., Нероева Н.В., Кармокова А.Г., Рябина М.В., Куликова И.Г., 20222022Нероев В.В., Балацкая Н.В., Нероева Н.В., Кармокова А.Г., Рябина М.В., Куликова И.Г.Neroev V.V., Balatskaya N.V., Neroeva N.V., Karmokova A.G., Ryabina M.V., Kulikova I.G.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/2351

Цитокины играют важную роль в патогенезе возрастной макулярной дегенерации (ВМД). Особый интерес представляют поздние стадии данного заболевания, которые являются основной причиной прогрессирующего снижения зрения. Терапевтический эффект изменений концентраций цитокинов после лечения также требует изучения как в краткосрочной, так и в долгосрочной перспективе, в особенности при возникновении атрофии на фоне антиангиогенной терапии. Цель: провести исследование комплекса 45 цитокинов различного биологического действия в сыворотке крови (СК) и слезной жидкости (СЖ) пациентов с влажной и атрофической ВМД.

В исследование были включены 70 человек (85 глаз) c 3-4 стадией ВМД по AREDS. В зависимости от формы ВМД, были сформированы 3 группы: I-я группа (n = 24) – пациенты с «географической атрофией», II-я группа (n = 22) – пациенты с макулярной атрофией на фоне антиангиогенной терапии влажной ВМД, III-я группа (n = 24) – пациенты с влажной формой, ранее не получавших лечение. Контрольную группу составили здоровые добровольцы (n = 25). Все группы были сопоставимы по возрасту и полу. Пациентам было проведено комплексное офтальмологическое обследование для постановки диагноза. Мультиплексное исследование локального (в СЖ) и системного (в СК) цитокинового статуса проводилось на приборе MAGPIX (платформа хMAP, Luminex Corporation, США) в программе Luminexx PONENT 3.1, наборами Procarta Plex (eBioscience, Австрия). Определялись 45 цитокинов различного биологического действия IL-1á, IL-1â, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL- 9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, IL-31, IFNá, IFNã, IL-8/ CXCL8, IP-10/CXCL10, SDF-1á/CXCL12, MCP-1/CCL2, MIP-1á/CCL3, MIP-1â/CCL4, RANTES/ CCL5, Eotaxin/CCL11, TNFá, TNFâ, GM-CSF, VEGF-A, VEGF-D, FGF-2, EGF, PDGF-BB, HGF, SCF, GRO-á, NGF-â, BDNF, LIF, PIGF-1.

Проведен скрининг широкой линейки цитокинов различного биологического действия в СК и СЖ пациентов с атрофической и влажной формами ВМД. Показано, что поздние стадии заболевания ассоциируются с локальными и системными нарушениями в звеньях про-/противовоспалительных медиаторов (IL-1â, IL-1ra, IL-18, LIF), хемоаттрактантных цитокинов (IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, MIP-1á/CCL3, MIP-1â/CCL4, RANTES/CCL5, Eotaxin/CCL11), регуляторов гемопоэза (IL-7) и факторов роста с ангиогенной активностью (EGF, HGF, PDGF-BB, VEGF-А). Изменения концентраций ряда хемокинов IP-10/CXCL10, SDF-1á/CXCL12, MIP-1á/CCL3, MIP-1â/CCL4, RANTES/CCL5 и Eotaxin/CCL11 (р < 0,05) в СК пациентов с атрофической и влажной формами ВМД могут представлять интерес для поиска биомаркеров, связанных с различными клиническими фенотипами заболевания, а также могут оказать помощь в разработке новых терапевтических стратегий лечения.

Cytokines play an integral role in pathogenesis of age-related macular degeneration (AMD). Of particular interest are the late stages of this disease, which causes progressive visual impairment. Therapy-induced effects of post-treatment cytokine concentrations also need to be studied, both at long and short observation terms. These studies are of vital importance if the atrophy occurs during antiangiogenic therapy. Our purpose was to study an array of 45 cytokines, in blood serum (BS) and lacrimal liquid (LL) of the patients with wet and atrophic AMD.

The study included 70 people (85 eyes) with stage 3-4 AMD according to AREDS. Depending on the form of AMD, 3 groups were discerned: I group (n = 24) included the patients with “geographic atrophy”; II group (n = 22), consisted of the patients with macular atrophy treated with antiangiogenic therapy of wet AMD; III group (n = 24), comprised the patients with a wet AMD who did not previously receive the treatment. Control group consisted of healthy volunteers (n = 25). All the groups were comparable for age and gender. The patients underwent a comprehensive ophthalmological examination to make a diagnosis. A multiplex study of the local (in the BS) and systemic (in the LL) cytokine status was carried out on a MAGPIX device (platform хMAP, Luminex Corporation, USA) in the Luminexx PONENT 3.1 software, using Procarta Plex kits (eBioscience, Austria). We determined 45 cytokines causing various biological effects, i.e., IL-1á, IL-1â, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, IL-31, IFNá, IFNã, IL-8/CXCL8, IP-10/CXCL10, SDF-1á/CXCL12, MCP-1/CCL2, MIP-1á/CCL3, MIP-1â/ CCL4, RANTES/CCL5, Eotaxin/CCL11, TNFá, TNFâ, GM-CSF, VEGF-A, VEGF-D, FGF-2, EGF, PDGF-BB, HGF, SCF, GRO-á, NGF-â, BDNF, LIF, PIGF-1.

Screening of a wide range of cytokines showing various biological effects was carried out in BS and LL of patients with atrophic and wet forms of AMD. It has been shown that the late stages of the disease are associated with local and systemic changes of pro / anti-inflammatory mediators (IL-1â, IL-1ra, IL-18, LIF), chemoattractant cytokines (IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, MIP-1á/CCL3, MIP-1â/ CCL4, RANTES/CCL5, Eotaxin/CCL11), hematopoietic regulators (IL-7), and growth factors with known angiogenic activity (EGF, HGF, PDGF-BB, VEGF-A). Altered concentrations of numerous chemokines, e.g., IP-10/CXCL10, SDF-1á/CXCL12, MIP-1á/CCL3, MIP-1â/CCL4, RANTES/CCL5 and Eotaxin/CCL11 (p < 0.05) in BS of the patients with atrophic and wet AMD may be of interest for the search of biomarkers associated with various clinical phenotypes of the disease and may be also helpful for development of new therapeutic strategies.

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