Роль цитокинов в патогенезе глазных болезней

Cytokines are a group of regulatory protein mediators. They perform a key role in the development and regulation of inflammatory response, reparative and plastic processes. Cytokines are an important part of humoral immunity and can be synthesized by a variety of cells. On the organism level cytokines create a complex selfregulating system, collectively referred to as the cytokine network. This review provides a brief history of cytokines development, from the first experiments of Coley W. to the introduction of modern classification. The review describes cytokine families that are most frequently studied in the ophthalmologic researches; studies of local and system cytokine profile changes in patients with eye diseases are summed up. Reviewed clinical and laboratory studies relate the influence of different cytokine groups on the inflammation process in patients with various forms of uveitis, effect of cytokines on the development of glaucomatous optic neuropathy and cytokines’ role in other ophthalmic diseases. These researches allow a better understanding of the mechanism of ocular immune privilege and study of ocular diseases pathogenesis on the molecular level. Cytokine research also helped discover the chronic inflammatory component of primary open-angle glaucoma and keratoconus, explain different kinds of inflammatory response in secondary uveitis, and discover new prognostic methods. This new data enables the development of new methods of pathogenetically oriented eye diseases therapy.Цитокины — группа белковых медиаторов, выполняющих регуляторную функцию. Они играют ключевую роль в развитии и регулировании защитной воспалительной реакции, а также пластических и репаративных процессов. Цитокины синтезируются множеством клеток и являются важным звеном гуморального иммунитета. На уровне организма цитокины представлены сложной саморегулирующейся системой, которую объединяют под понятием цитокиновой сети. В обзоре представлена краткая история развития исследований цитокинов от первых опытов W. Coley до введения современной классификации. Описаны наиболее часто исследуемые в офтальмологии семейства цитокинов, дан обзор научных работ, посвященных изменению системного и локального цитокинового профиля при глазных заболеваниях. Описано влияние различных групп цитокинов на механизмы внутриглазного воспаления при различных видах увеита. Дан обзор клинических и лабораторных исследований роли цитокинов при развитии глаукомной оптической нейропатии и ряда других офтальмопатологий. Благодаря исследованиям такого рода стало возможным понимание механизмов иммунной привилегированности органа зрения и изучение патогенеза большинства известных глазных заболеваний на молекулярном уровне. Так, во многом благодаря исследованиям цитокинов был обнаружен хронический воспалительный компонент при первичной открытоугольной глаукоме и кератоконусе, объяснены различные варианты течения воспаления при вторичных увеитах, открыты новые прогностические методики. Развитие области знаний о роли цитокинов при офтальмопатологии сделало возможным появление новых направлений патогенетически ориентированной терапии глазных заболеваний

Сравнительный химический анализ внутриглазной жидкости и тканей дренажной зоны глаза при первичной открытоугольной глаукоме

PURPOSE: There are two primary aims of this study:1. To perform a comparative chemical analysis of aqueous humour (AH), scleral tissue, and trabecular meshwork in patients with primary open-angle glaucoma (POAG).2. To evaluate the tissue’s chemical composition at the different POAG stages and with in patients with pseudoexfoliation glaucoma (PEG).METHODS: The concentration of certain chemical elements — carbon (C), nitrogen (N), oxygen (O), aluminum (Al), calcium (Ca), chlorine (Cl), potassium (K), magnesium (Mg), sodium (Na), phosphorus (P), silicon (Si), sulfur (S) — was determined in the dried AH residue, trabecular meshwork and sclera biopsy samples obtained from patients with POAG (stage I and II), patients with pseudoexfoliation glaucoma (PEG), and patients with POAG without pseudoexfoliation material (PEM). Samples were analyzed using a scanning electron microscope (SEM) EVO LS 10 (“Zeiss”,Germany). The chemical composition study was performed with an energy-dispersive spectrometer (EDS) Oxford-XMAX-50 (“Oxford”,UK) in a low-vacuum mode (70 Pa) with an accelerating voltage of 21.5 kV.RESULTS: In the case of POAG (stage I and II) patients, there were significant differences in Cl distribution in dried AH residue and Si distribution in the trabecular meshwork. In the case of pseudoexfoliative glaucoma (PEG) and patients with POAG without PEM, there was a difference in the N distribution in dried AH residue, as well as Ca, Cl, and Na distribution in the trabecular meshwork. During scleral tissue comparative chemical analysis, no significant changes in studied elements’ concentration between patient groups were evident.CONCLUSION: Changes between stage II of POAG and stage III of POAG patient groups may indicate that there is an increase in the electrolyte and acid-base imbalance associated with the progression of the disease. Differences in chemical elements distribution in patients with PEG and in patients with POAG without PEM result from the molecular structure of PEM. The tissue’s water and salt balance and molecular chemical composition alterations provide the following insights for future research in finding the optimal treatment method for patients with all stages and types of glaucoma.ЦЕЛЬ. Провести сравнительный химический анализ внутриглазной жидкости (ВГЖ), склеры и трабекулы при первичной открытоугольной глаукоме (ПОУГ). Оценить химический состав тканей при различных стадиях ПОУГ, а также при псевдоэксфолиативной глаукоме (ПЭГ).МЕТОДЫ. Определено содержание ряда химических элементов: углерода (С), азота (N), кислорода (O), алюминия (Al), кальция (Са), хлора (Cl), калия (К), магния (Mg), натрия (Na), фосфора (P), кремния (Si), серы (S) в сухом веществе ВГЖ, биоптатах трабекулярной ткани и склеры у пациентов со II и III стадиями ПОУГ, а также у пациентов с ПЭГ и ПОУГ без псевдоэксфолиативного материала. Визуализация проводилась с помощью сканирующего электронного микроскопа (СЭМ) ЕVO LS 10 («Zeiss», Германия), исследование химического состава осуществлялось на энергодисперсионном спектрометре (ЭДС) Oxford-X-MAX-50 («Oxford», Великобритания) в режиме низкого вакуума (70 Па) при ускоряющем напряжении 21,5 кВ.РЕЗУЛЬТАТЫ. Выявлены различия в распределении Сl в сухом веществе ВГЖ и Si в трабекуле у пациентов со II и III стадиями ПОУГ. При сравнительном анализе тканей пациентов с ПЭГ и ПОУГ без псевдоэксфолиативного материала (ПЭМ) показано различие в распределении N сухого вещества ВГЖ, а также Ca, Cl, Na трабекулы. При сравнительном анализе элементного состава склеры между указанными группами статистически значимых различий в распределении исследуемых элементов выявлено не было.ЗАКЛЮЧЕНИЕ. Изменения, выявленные при сравнении II и III стадий ПОУГ, могут свидетельствовать о нарастании электролитного и кислотно-основного дисбаланса при прогрессировании заболевания. Отличия в распределении элементов между группами ПОУГ без ПЭМ и ПЭГ обусловлены молекулярным строением ПЭМ. Различия в водно-солевом и молекулярно-химическом составе тканей следует учитывать в дальнейших исследованиях, направленных на поиск оптимального медикаментозного метода лечения пациентов с разными стадиями и формами глаукомы

СПОСОБЫ МОДЕЛИРОВАНИЯ ГЛАУКОМНОЙ ОПТИЧЕСКОЙ НЕЙРОПАТИИ В ЭКСПЕРИМЕНТЕ НА КРЫСАХ

Experimental in vivo glaucoma models allow expanding the knowledge of the glaucomatous optic neuropathy pathogenesis. An important criterion of choosing an experimental animal model is the ability to extrapolate received data to humans. This review covers main models of experimental glaucoma in rodents and its technology, including rodent anatomy and physiology specifics. Using rats in glaucoma modeling offers the advantage of fast disease progression and ease of use. Genetic models are based on congenital impairment of intraocular hydrodynamics due to gene mutation; induced models refer to artificial intraocular pressure (IOP) elevation or initiation of neuropathy without affecting the aqueous outflow. Methods aimed at hydrodynamics alteration lead to IOP increase and thus to glaucomatous optic neuropathy development. These include thermic, mechanical and laser effects on the aqueous humor outflow. Optic neuropathy without affecting IOP can be caused by mechanical impairment of the optic nerve, ischemia followed by reperfusion, excitotoxicity, or intravitreal injection of endothelin-1 or rose bengal with following photostimulation. Genetic glaucoma models include rodents with congenital impairment of eye drainage zone due to gene mutations, such as DBA gene family and α1-subunits of I-type collagen mutation, synthesis of altered myocilin or calcitonin receptorlike receptor expression. The current range of rodent glaucoma modelling methods is a perspective and important part of in vivo studies, related to glaucoma pathogenesis and treatment.Использование экспериментальных моделей глаукомы in vivo позволяет расширить знания о патогенезе развития глаукомной оптической нейропатии (ГОН). Важным критерием выбора экспериментального животного является возможность экстраполяции экспериментальных данных на человека. В обзоре рассмотрены основные модели экспериментальной глаукомы на грызунах, а также особенности техники выполнения с учетом их анатомии и физиологии. Использование крыс в моделировании глаукомы обладает такими преимуществами, как доступность и быстрое прогрессирование заболевания. Различают генетические модели, основанные на врожденном нарушении гидродинамики вследствие мутации генов, и индуцированные модели, к которым относятся повышение внутриглазного давления (ВГД) и инициирование нейропатии без влияния на офтальмотонус. Методы, основанные непосредственно на воздействии на гидродинамику глаза, приводят к повышению офтальмотонуса и последующему развитию ГОН. К ним относят термическое, механическое и лазерное воздействие на пути оттока. Оптическая нейропатия без повышения ВГД может быть смоделирована с помощью механического повреждения зрительного нерва, ишемии с последующей реперфузией, эксайтотоксического фактора, а также интравитреального введения эндотелина-1 или бенгальского розового с последующей фотостимуляцией. В генетических моделях используются грызуны с врожденными изменениями в дренажной системе глаза из-за мутаций семейства DBA и α1-субъединицы коллагена I типа, синтеза измененного миоциллина, экспрессии кальцитонинподобного рецептора, что приводит к развитию стойкой ГОН. Имеющийся к настоящему моменту широкий спектр методик воспроизведения глаукомного процесса у грызунов является перспективным и важным элементом исследований in vivo, посвященных патогенезу и лечению глаукомы

CORNEAL GRAFT REJECTION AFTER KERATOPLASTY

Corneal transplantation is a method of surgical treatment used to restore the optical and structural properties of the diseased cornea which is successfully performed for over 100 years. The immune rejection remains one of the most common causes of an unsatisfactory outcomes of penetrating keratoplasty. The cases of corneal allograft rejection range from 2.3% to 65% depending on the risk factors taking place in the recipient. The most well-known risk factors for corneal allograft rejection are neovascularization of the recipient’s cornea, active ocular inflammation, herpetic keratitis, ocular surface disease, young age, previous surgery of the anterior segment of the eye, neurotrophic keratopathy, big and eccentric graft, anterior synechia. Given the fact that the pathophysiology of corneal graft rejection is very complex and not fully understood the applied methods of treatment and prevention are often ineffective in “high risk” patients. New experimental targeted approaches including the use of antibodies and gene therapy are currently being developed but do not have a clear success in the clinic yet.Therefore for obtaining satisfactory outcomes of corneal transplantation in “high risk” patients all main known risk factors have to be taken into account with subsequent possible preoperative therapy to reduce their impact; careful monitoring of the patient in the postoperative period should be done to early detection of allograft rejection signs; optimal schemes and combinations of immunosuppressive drugs authorized for use in the clinic have to be developed

Incidence and risk factors for persistent symptoms in adults previously hospitalised for COVID-19

Background: The long-term sequalae of COVID-19 remain poorly characterized. We assessed persistent symptoms in previously hospitalized patients with COVID-19 and assessed potential risk factors. Methods: Data were collected from patients discharged from 4 hospitals in Moscow, Russia between 8 April and 10 July 2020. Participants were interviewed via telephone using an ISARIC Long-term Follow-up Study questionnaire. Results: 2,649 of 4755 (56%) discharged patients were successfully evaluated, at median 218 (IQR 200, 236) days post-discharge. COVID-19 diagnosis was clinical in 1291 and molecular in 1358. Most cases were mild, but 902 (34%) required supplemental oxygen and 68 (2.6%) needed ventilatory support. Median age was 56 years (IQR 46, 66) and 1,353 (51.1%) were women. Persistent symptoms were reported by 1247 (47.1%) participants, with fatigue (21.2%), shortness of breath (14.5%) and forgetfulness (9.1%) the most common symptoms and chronic fatigue (25%) and respiratory (17.2%) the most common symptom categories. Female sex was associated with any persistent symptom category OR 1.83 (95% CI 1.55 to 2.17) with association being strongest for dermatological (3.26, 2.36 to 4.57) symptoms. Asthma and chronic pulmonary disease were not associated with persistent symptoms overall, but asthma was associated with neurological (1.95, 1.25 to 2.98) and mood and behavioural changes (2.02, 1.24 to 3.18), and chronic pulmonary disease was associated with chronic fatigue (1.68, 1.21 to 2.32). Conclusions: Almost half of adults admitted to hospital due to COVID-19 reported persistent symptoms 6 to 8 months after discharge. Fatigue and respiratory symptoms were most common, and female sex was associated with persistent symptoms.</p

Incidence and risk factors for persistent symptoms in adults previously hospitalized for COVID-19

Background: The long-term sequalae of COVID-19&nbsp;remain poorly characterized. We assessed persistent symptoms in previously hospitalized patients with COVID-19 and assessed potential risk factors. Methods: Data were collected from patients discharged from 4&nbsp;hospitals in Moscow, Russia between 8 April and 10&nbsp;July 2020. Participants were interviewed via telephone using an ISARIC Long-term Follow-up Study questionnaire. Results: 2,649 of 4755 (56%) discharged patients were successfully evaluated, at median 218 (IQR 200, 236) days post-discharge. COVID-19 diagnosis was clinical in 1291 and molecular in 1358. Most cases were mild, but 902 (34%) required supplemental oxygen and 68 (2.6%) needed ventilatory support. Median age was 56&nbsp;years (IQR 46, 66) and 1,353 (51.1%) were women. Persistent symptoms were reported by 1247 (47.1%) participants, with fatigue (21.2%), shortness of breath (14.5%) and forgetfulness (9.1%) the most common symptoms and chronic fatigue (25%) and respiratory (17.2%) the most common symptom categories. Female sex was associated with any persistent symptom category OR 1.83 (95% CI 1.55 to 2.17) with association being strongest for dermatological (3.26, 2.36 to 4.57) symptoms. Asthma and chronic pulmonary disease were not associated with persistent symptoms overall, but asthma was associated with neurological (1.95, 1.25 to 2.98) and mood and behavioural changes (2.02, 1.24 to 3.18), and chronic pulmonary disease was associated with chronic fatigue (1.68, 1.21 to 2.32). Conclusions: Almost half of adults admitted to hospital due to COVID-19 reported persistent symptoms 6 to 8&nbsp;months after discharge. Fatigue and respiratory symptoms were most common, and female sex was associated with persistent symptoms

Incidence and risk factors for persistent symptoms in adults previously hospitalised for COVID-19

Background: The long-term sequalae of COVID-19 remain poorly characterised. We assessed persistent symptoms in previously hospitalised patients with COVID-19 and assessed potential risk factors. Methods: Data were collected from patients discharged from 4 hospitals in Moscow, Russia between April 8 and July 10, 2020. Participants were interviewed via telephone using an ISARIC Long-term Follow-up Study questionnaire. Results: 2,649 of 4755 (56%) discharged patients were successfully evaluated, at median 218 (IQR 200, 236) days post-discharge. COVID-19 diagnosis was clinical in 1291 and molecular in 1358. Most cases were mild, but 902 (34%) required supplemental oxygen and 68 (2.6%) needed ventilatory support. Median age was 56 years (IQR 46, 66) and 1,353 (51.1%) were women. Persistent symptoms were reported by 1247 (47.1%) participants, with fatigue (21.2%), shortness of breath (14.5%) and forgetfulness (9.1%) the most common symptoms and chronic fatigue (25%) and respiratory (17.2%) the most common symptom categories. Female sex was associated with any persistent symptom category OR 1.83 (95% CI 1.55 to 2.17) with association being strongest for dermatological (3.26, 2.36 to 4.57) symptoms. Asthma and chronic pulmonary disease were not associated with persistent symptoms overall, but asthma was associated with neurological (1.95, 1.25 to 2.98) and mood and behavioural changes (2.02, 1.24 to 3.18), and chronic pulmonary disease was associated with chronic fatigue (1.68, 1.21 to 2.32). Conclusions: Almost half of adults admitted to hospital due to COVID-19 reported persistent symptoms 6 to 8 months after discharge. Fatigue and respiratory symptoms were most common, and female sex was associated with persistent symptoms