Effective regeneration of damaged soft orbital tissues in Graves ophthalmopathy (GO) requires coordinated remodeling of the extracellular matrix. Matrix metalloproteinases (MMPs) play an important role in the synthesis and degradation homeostasis of extracellular matrix components in various physiological and pathological conditions. Their proteolytic activity is inhibited by tissue inhibitors of metalloproteinases (TIMP). The biochemical processes taking place in extraocular muscles and retrobulbar tissue fibrogenesis in GO are not fully understood. Aims to assess some biochemical mechanisms of extraocular muscles and retrobulbar tissue fibrogenesis in GO patients. Material and methods. The study included 65 people (130 eyes) at the age of 43 (3550) years. Three groups of subjects were formed: 32 patients with a moderate GO severity (clinical group), 18 patients with autoimmune thyroid pathology without GO (comparison group), and 15 healthy persons (control). The diagnosis was based on clinical, laboratory, and instrumental data. A comprehensive ophthalmologic examination and blood sampling for determination of MMP-1, -13, TIMP-1, sulfated glycosaminoglycans (sGAG) and antibodies to thyroid-stimulating hormone receptor (TSHRAbs) were conducted. The data were statistically processed using the program Statistica 10.0. Results. An elevated level of MMP-13, observed in all GO patients (p0.05). For the active phase of GOP, the comparison with the control group showed a 3.5-fold increase in MMP-13 (p0.001) and 1.17-fold rise in TIMP-1 (p0.05). Pulse glucocorticoid therapy reduced MMP-13 by 48.6% (p0.001), TIMP-1 by 2.7% (p0.001), and TSHRAbs by 93% (p0.001) compared with active GO, but these indicators were higher than the reference limits of control (p0.05). In inactive GO, despite increased MMP-13, TIMP-1 decreased to the reference values (p=0.533). There were no significant differences in MMP-1 in groups of subjects (p=0.865). Conclusions. We have found imbalance between MMP-13 and TIMP-1 production in different activity phases of GO. Active GO is characterized by an increase in serum MMP-13 and TIMP-1. Dysregulation of intercellular matrix remodeling, possibly, underlies the development of extraocular muscles and retrobulbar tissue fibrosis in GO.
НАЗВАНИЕ СТАТЬИМорфофункциональная характеристика и иммунологическая регуляция функции орбитальных фибробластов при эндокринной офтальмопатии АВТОРЫ Е.С. Таскина *, С.В. Харинцева ОРГАНИЗАЦИИ ФГБОУ ВО Читинская государственная медицинская академия, Чита, Россия РЕЗЮМЕ Эндокринная офтальмопатия (ЭОП) -это хроническое заболевание, характеризующееся прогрессирующим аутоиммунным воспалением мягких ретробульбарных тканей. В патогенезе инфильтративного процесса и фиброзирования экстраокулярных мышц и/или ретробульбарной клетчатки важное значение имеют орбитальные фибробласты, обладающие уникальными морфофункциональными свойствами. Они, в отличие от фибробластов других локализаций, имеют не мезодермальное, а нейро-экдодермальное происхождение. В обзоре рассматриваются иммунологические аспекты регулирования функции данных клеток в разные фазы активности заболевания. Межклеточное взаимодействие с Т-лимфоцитами (CD40-CD154) приводит к активации орбитальных фибробластов с усилением экспрессии патологических рецепторов к тиреотропному гормону, а также продукции компонентов межклеточного матрикса, молекул адгезии, ростовых факторов, цитокинов и простагландинов. Дана подробная морфофункциональная характеристика отдельных субпопуляций фибробластов орбиты и механизмы регуляции их трансдифференцировки в адипоциты и миофибробласты. Представлен анализ литературных данных по влиянию T-хелперов 17 типа на функциональную активность Thy1+/Thy1-(CD90+/CD90) орбитальных фибробластов. Отмечена важность дальнейшего изучения особенностей фибробластов орбиты при ЭОП и их межклеточного взаимодействия с различными иммунными клетками, что, возможно, сможет раскрыть новые патогенетические механизмы изучаемой патологии. Ключевые слова: эндокринная офтальмопатия, патогенез, орбитальные фибробласты. TITLE Morphofunctional characteristics and immunological regulation of the orbital fibroblasts function in endocrine ophthalmopathy AUTHORS ABSTRACT Clinical and experimental thyroidology.Endocrine ophthalmopathy (EOP) is a chronic disease characterized by progressive autoimmune inflammation of the soft retrobulbar tissues in thyroid dysfunction. The orbital fibroblasts with their unique morphofunctional properties are very important in the pathogenesis of the infiltrative process and fibrosis of the extraocular muscles and / or retrobulbar tissue, They, unlike other localization fibroblasts, have not mesodermal, but neuro-ectodermal origin. The review acquaints with the immunological aspects of the regulation of these cells in different activity phases of disease. Intercellular interaction with T-lymphocytes (CD40-CD154) leads to orbital fibroblasts activation with increased expression of pathological receptors for thyroid-stimulating hormone, as well as production of intercellular matrix components, adhesion molecules, growth factors, cytokines and prostaglandins. Detailed morphofunctional characteristics of the orbit fibroblast subpopulations and mechanisms regulating their transdifferentiation into adipocytes and myofibroblasts are given. The analys...
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