Abstract
Diabetic retinopathy (DR) is multifactorial by its origin, involving many cytokines and growth factors. Studies of cytokine levels in biological fluids seem to be relevant for an in-depth understanding of the disease pathogenesis. The purpose of the work was a comparative analysis of 45 cytokines at systemic (blood serum (BS)) and local (vitreous humor (VH)) levels in the patients with complicated proliferative DR, showing various features of the clinical pattern. The content of cytokines was tested in 53 samples of BS and 32 samples of VH in 53 patients with type 1 and type 2 diabetes mellitus with severe proliferative DR. We used the multiplex analysis technique by means of xMAP platform and Luminex xPONENT 3.1 program using 45-plex sets (Procarta Plex «eBioscience», Austria). 25 cytokines were detected at significant amounts in BS test samples, and 27 cytokines were revealed in VH specimens. Sensitivity limits of the test system allowed to find significantly higher levels of 7 cytokines (IL-6, IL-8, IP-10, MCP-1, HGF, LIF and VEGF-A) in VH samples, than in the BS, thus indicating to their local intraocular production. Correlations between the contents of VEGF-A growth factor and amounts of cytokines, including those involved in inflammatory reactions, are shown in VH, thus presuming the interrelation of pathogenetic components, i.e., inflammation and neoangiogenesis. The features of intraocular cytokine content were determined for various manifestations of diabetic ocular changes. Hemophthalmus has been shown to be associated with increased IL-8 and IP-10; iris rubeosis, with increase in LIF; proliferative DR activity was associated with higher MCP-1 levels, and extremely severe changes were related to increase in IL-6 and EGF. Testing of cytokines in biological fluids is informative when studying the mechanisms of inflammation, neoangiogenesis, and protective responses in pathogenesis of diabetic retinopathy.
Highlights
Медицинская Иммунология Medical Immunology (Russia)/Meditsinskaya Immunologiya the disease pathogenesis
The purpose of the work was a comparative analysis of 45 cytokines at systemic (blood serum (BS)) and local (vitreous humor (VH)) levels in the patients with complicated proliferative Diabetic retinopathy (DR), showing various features of the clinical pattern
The content of cytokines was tested in 53 samples of BS and 32 samples of VH in 53 patients with type 1 and type 2 diabetes mellitus with severe proliferative DR
Summary
Нероев В.В., Зайцева О.В., Балацкая Н.В., Лазутова А.А. ФГБУ «Национальный медицинский исследовательский центр глазных болезней имени Гельмгольца» Министерства здравоохранения РФ, Москва, Россия. Изучение уровней цитокинов в биологических жидкостях представляется актуальным с целью углубленного понимания патогенеза заболевания. Цель работы – сравнительный анализ системных (сыворотка крови (СК)) и локальных (стекловидное тело (СТ)) уровней 45 цитокинов у пациентов с осложненной пролиферативной ДР, а также при различных особенностях клинической картины заболевания. Показаны корреляционные связи между содержанием в СТ ростового фактора VEGF-A и ряда цитокинов, в том числе участвующих в воспалительных реакциях, что свидетельствует о взаимосвязи звеньев патогенеза: воспаления и неоангиогенеза. Показана связь гемофтальма с повышением IL-8 и IP-10, рубеоза радужки – с повышением LIF, активности пролиферативной ДР – с увеличением MCP-1, крайне тяжелых изменений – с ростом IL-6 и EGF. Тестирование цитокинов в биологических жидкостях информативно при изучении механизмов воспаления, неоангиогенеза, а также защитных реакций в патогенезе ДР. Ключевые слова: сахарный диабет, диабетическая ретинопатия, тракционная отслойка сетчатки, гемофтальм, рубеоз радужки, патогенез, цитокины, стекловидное тело, сыворотка крови. Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russian Federation
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