ophthalmologyОфтальмологияOphthalmology in Russia1816-50952500-0845Ophthalmology10.18008/1816-5095-2021-2-198-207ophthalmology-1533Research ArticleОБЗОРЫREVIEWSДендритное ветвление ганглиозных клеток сетчатки как биомаркер глаукомной оптической нейропатии и болезни Альцгеймера и мишень нейропротекторной терапииDendritic Branching of Retinal Ganglion Cells as a Biomarker of Glaucomatous Optic Neuropathy and Alzheimer’s Disease and a Target of Neuroprotective Therapyhttps://orcid.org/0000-0002-0161-5010ЗуеваМ. В.ZuevaM. V.

доктор биологических наук, профессор, начальник отдела клинической физиологии зрения им. С.В. Кравкова,

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

Doctor of biological sciences, Professor, head of the Department of clinical physiology of vision named after S.V. Kravkov,

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

visionlab@yandex.ruhttps://orcid.org/0000-0001-8381-2124ЖуравлеваА. Н.ZhuravlevaA. N.

кандидат медицинских наук, научный сотрудник отдела глаукомы,

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

PhD, researcher, Glaucoma department,

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

https://orcid.org/0000-0002-6327-3546БоголеповаА. Н.BogolepovaA. N.

доктор медицинских наук, профессор, профессор кафедры неврологии, нейрохирургии и медицинской генетики, руководитель отдела когнитивных нарушений,

ул. Островитянова, 1, Москва, 117997,

ул. Островитянова, 1, стр. 10, Москва, 117997

MD, Professor of the Neurology department, head of the cognitive impairment Department,

Ostrovityanova str., 1, Moscow, 117997, 

Ostrovityanova str., 1/10, Moscow, 117997

ФГБУ «Национальный медицинский исследовательский центр глазных болезней им. Гельмгольца» Министерства здравоохранения Российской ФедерацииРоссияHelmholtz National Medical Research Center of Eye DiseasesRussian FederationФГАОУ ВО «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской Федерации; ФГБУ «Федеральный центр мозга и нейротехнологий» Федерального медико-биологического агентства РоссииРоссияPirogov Russian National Research Medical University; Federal Center of Brain Research and NeurotechnologiesRussian Federation202103072021182198207Copyright © Зуева М.В., Журавлева А.Н., Боголепова А.Н., 20212021Зуева М.В., Журавлева А.Н., Боголепова А.Н.Zueva M.V., Zhuravleva A.N., Bogolepova A.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.ophthalmojournal.com/opht/article/view/1533

Необратимое повреждение структуры аксонов и гибель сомы ганглиозных клеток сетчатки (ГКС) при первичной открытоугольной глаукоме (ПОУГ) и болезни Альцгеймера (БА) развиваются на фоне уже имеющейся клинической манифестации, которой предшествует медленный период прогрессивной потери синапсов и дендритов ГКС. Недавние исследования показывают, что целостность дендритного ветвления ГКС может служить и мишенью нейропротекторной терапии, и чувствительным маркером дегенерации сетчатки при БА и глаукоме. Для разработки методов комплексной нейропротекторной терапии необходимо обосновать мишени и тактику воздействия на дендритное дерево ГКС, ремоделирование которого, по современным представлениям, может быть тесно и антагонистически связано с регенерацией аксона после его повреждения при травмах и нейродегенеративных заболеваниях. ГКС обладают высокой способностью к функциональной модификации. В настоящее время доказана перспективность применения нейропротекторных препаратов и нейротрофинов для поддержания адаптивной пластичности ГКС и восстановления их синаптических контактов на уровне сетчатки и мозга. Понимание особенностей адаптивной пластичности ГКС при БА и глаукоме позволит использовать в доклинических стадиях этих заболеваний технологии, направленные на активацию внутреннего потенциала ремоделирования нейронов, включая модификацию дендритного ветвления ГК и регенерацию их аксонов. Повышение знаний о последовательности и механизмах ранних событий во внутреннем плексиформном слое сетчатки будет способствовать разработке таргетной нейропротекторной терапии и новых технологий для раннего обнаружения ПОУГ, БА и, возможно, других системных и локальных нейродегенеративных состояний. 

Irreversible damage to the structure of axons and death of the retinal ganglion cell (RGC) soma in primary open-angle glaucoma (POAG) and Alzheimer’s disease (AD) develop against the background of the already existing clinical manifestation, which is preceded by a slow period of progressive loss of synapses and dendrites of the RGCs. Recent studies have shown that the integrity of the RGC’s dendritic branching can serve as both a target of neuroprotective therapy and a sensitive marker of retinal degeneration in AD and glaucoma. To develop methods of complex neuroprotective therapy, it is necessary to substantiate the targets and tactics of affecting the dendritic tree of the RGCs, the remodeling of which, according to modern concepts, can be closely and antagonistically related to the regeneration of the axon after its damage in trauma and neurodegenerative diseases. RGCs are highly capable of functional modification. Currently, it has been proven that the use of neuroprotective drugs and neurotrophins is promising for maintaining the adaptive plasticity of RGCs and restoring their synaptic contacts at the level of the retina and brain. Understanding the features of the adaptive plasticity of RGCs in AD and glaucoma will make possible to use technologies to activate the internal potential of neuronal remodeling, including the modification of dendritic branching of RGCs and regeneration of their axons, in the preclinical stages of these diseases. Increasing knowledge about the sequence and mechanisms of early events in the retina’s inner plexiform layer will contribute to the development of targeted neuroprotective therapy and new technologies to detect early POAG, AD, and, possibly, other systemic and local neurodegenerative conditions. 

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