glazmagThe EYE ГЛАЗThe EYE GLAZ2222-44082686-8083Академия медицинской оптики и оптометрии10.33791/2222-4408-2022-2-32-45glazmag-335Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESСравнительные аспекты экспериментальных моделей неоваскуляризации глаз различной локализации (экспериментальные исследования)Comparative aspects of experimental models of eye neovascularization of different localization (experimental studies)https://orcid.org/0000-0003-2708-7217ЛихванцеваВ. Г.LikhvantsevaV. G.

Лихванцева Вера Геннадьевна, доктор медицинских наук, профессор кафедры офтальмологии; старший научный сотрудник 

123098, Москва, ул. Гамалеи, д. 15

125371, Москва, Волоколамское ш., д. 91

Vera G. Likhvantseva, Dr. Sci. (Med.), Professor; Senior Research Fellow 

15, Gamalei Str., Moscow, 123098

91, Volokolamskoe Highway, Moscow, 125371

likhvantseva-4@yandex.ruГеворкянА. С.GevorgyanA. S.

Арминэ Сейрановна Геворкян, соискатель кафедры офтальмологии

125371, Москва, Волоколамское ш., д. 91

Armine S. Gevorgyan, Applicant for the Department of Ophthalmology 

91, Volokolamskoe Highway, Moscow, 125371

КапковаС. Г.KapkovaS. G.

Светлана Георгиевна Капкова, кандидат медицинских наук, заведующая отделением офтальмологии, доцент кафедры офтальмологии

123098, Москва, ул. Гамалеи, д. 15

125371, Москва, Волоколамское ш., д. 91

Svetlana G. Kapkova, Cand. Sci. (Med.), Head of the Department of Ophthalmology, Associate Professor

15, Gamalei Str., Moscow, 123098

91, Volokolamskoe Highway, Moscow, 125371

ФГБУ «Государственный научный центр Российской Федерации – Федеральный медицинский биофизический центр им. А.И. Бурназяна» ФМБА России; Академия постдипломного образования ФГБУ «Федеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий Федерального медико-биологического агентства»РоссияRussian State Research Center − Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency; Academy of Postgraduate Education of the Federal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of Federal Medical Biological Agency of RussiaRussian FederationАкадемия постдипломного образования ФГБУ «Федеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий Федерального медико-биологического агентства»РоссияAcademy of Postgraduate Education of the Federal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of Federal Medical Biological Agency of RussiaRussian Federation2022050720222423245Copyright © Академия медицинской оптики и оптометрии, 20222022Академия медицинской оптики и оптометрииАкадемия медицинской оптики и оптометрииhttps://www.theeyeglaz.com/jour/about/submissions#copyrightNoticehttps://www.theeyeglaz.com/jour/article/view/335

Постоянная эволюция лечебных технологий и меняющихся требований к ним диктует разработку стратегии их внедрения в клиническую практику. Первым этапом служит оценка возможностей, эффективности, достоинств и недостатков, отработка показаний и противопоказаний на моделях заболеваний глаз в эксперименте.

Цель работы

Цель работы: провести сравнительный анализ экспериментальных моделей неоваскуляризации глаз различной локализации, изучить их воспроизводимость и соответствие природным аналогам заболеваний человека.

Материал и методы

Материал и методы. В эксперименте были сформированы две модели неоангиогенеза хориоретинальной и две модели роговичной локализации. Все модели формировали на глазах одного биологического вида экспериментальных животных – кроликах породы советская шиншилла (n = 60). Далее эмпирическим путем анализировали достоинства и недостатки каждой из используемых моделей неоангиогенеза глаза. Соответствие сформированных экспериментальных моделей у животных природным заболеваниям человека проверяли методами флюоресцентной ангиографии, оптической когерентной томографии (ОКТ) и гистологическими методами исследований.

Результаты

Результаты. Все четыре экспериментальные модели продемонстрировали признаки неоваскуляризации с различными клиническими проявлениями, верифицированные ангиографически, морфометрически (модели № 1 и 2 по данным ОКТ; in vivo) и гистологически (модели № 1–4; ex vivo). Процент «выхода» неоваскуляризации на разных моделях варьировался от 75 до 100%. Модели хориоретинальной неоваскуляризации были ближе по клиническим проявлениям природным проявлениям неоваскулярной формы возрастной макулярной дегенерации (н-ВМД). Модели передней локализации были предпочтительнее из-за свободного доступа, легкости воспроизведения и хорошей визуализации зоны интереса, позволяющей выполнять мониторинг в ходе лечения; вместе с тем ангиогенез на этих моделях имеет другую природу и отчасти другие механизмы, в которых большую роль играют воспалительные реакции. Однако передняя локализация позволяет провести комплексную оценку патологического процесса с количественным подсчетом новообразованных сосудов в роговице, включая их длину, диаметр просвета, и оценить полноценность анатомии сосудистой стенки, состав и плотность паравазального клеточного микроокружения. В совокупности это имеет немаловажное значение в доклинических испытаниях технологий с заявленным ангиостатическим эффектом.

Заключение

Заключение. Для получения полноценного объема информации об испытуемом препарате с заявленным ангиостатическим потенциалом необходимо использовать несколько моделей неоангиогенеза с разными механизмами патогенеза, на которых можно изучить спектр их возможностей и побочных эффектов, а также оценить весь спектр биологических эффектов.

The evolution of treatment technologies and changing requirements for them dictates the development of a strategy for their implementation in clinical practice. The fi rst stage is the assessment of the capabilities, effectiveness, advantages and disadvantages, the development of indications and contraindications on models of eye diseases in the experiment.

The purpose of the work

The purpose of the work: to conduct a comparative analysis of experimental models of neovascularization of the eyes of different localization, their reproducibility and compliance with natural analogues of human diseases.

Material and methods

Material and methods. In an experiment 2 models of chorioretinal neoangiogenesis and 2 models of corneal localization were studied. All models employed the eyes of one biological species of experimental animals – rabbits of the Chinchilla breed (n = 60). Further, the advantages and disadvantages of each of the used models of eye neoangiogenesis were analyzed empirically. The correspondence of the formed experimental models in animals to natural human diseases was checked by fl uorescence angiography, optical coherence tomography and histological research methods.

Results

Results. All 4 experimental models demonstrated clinical signs of neovascularization with different clinical manifestations, verifi ed angiographically, morphometrically (OCT models 1 and 2; in vivo) and histologically (models 1–4; ex vivo). The percentage of neovascularization “yield” on different models varied from 75 to 100%. Models of chorioretinal neovascularization were closer in clinical manifestations to the natural manifestations of the neovascular form of age-related macular degeneration. However, anterior localization models were preferred because of the free access, ease of reproduction, and good visualization of the area of interest, allowing monitoring during treatment. At the same time, angiogenesis in these models has a different nature and partly other mechanisms in which infl ammatory reactions play an important role. However, these models make it possible to conduct a comprehensive assessment of the pathological process with a quantitative count of the newly formed vessels in the cornea, including their length, the diameter of their lumen, to assess the usefulness of the anatomy of the vascular wall, the composition and density of the paravasal cell microenvironment. Taken together, this is of no small importance in preclinical trials of technologies with the claimed angiostatic effect.

Conclusion

Conclusion. To obtain a full amount of information about the test drug with the declared angiostatic potential, it is necessary to use several models of neoangiogenesis with different mechanisms of pathogenesis, on which one can study the range of their capabilities and side effects, as well as evaluate the entire range of biological effects.

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