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Autophagy as a Target for the Retinoprotective Effects of the Mitochondria-Targeted Antioxidant SkQ1

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Abstract

Age-related macular degeneration (AMD) is a complex neurodegenerative disease, a main cause of vision loss in elderly people. The pathogenesis of dry AMD, the most common form of AMD (~ 80% cases), involves degenerative changes in the retinal pigment epithelium (RPE), which are closely associated with the age-associated impairments in autophagy. Reversion of these degenerative changes is considered as a promising approach for the treatment of this incurable disease. The purpose of our study was to assess the relationship between previously identified retinoprotective effects of the mitochondrial antioxidant plastoquinonyl-decyl-triphenylphosphonium (SkQ1) and its influence on the autophagy process in senescence-accelerated OXYS rats characterized by the development of AMD-like retinopathy (Wistar rats were used as a control). The treatment with SkQ1 (250 nmol/kg body weight) during the period of active disease progression (from 12 to 18 months of age) completely prevented progression of clinical manifestations of retinopathy in the OXYS rats, suppressed atrophic changes in the RPE cells and activated autophagy in the retina, which was evidenced by a significant decrease in the content of the multifunctional adapter protein p62/Sqstm1 and increase in the level of the Beclin1 gene mRNA. In general, the results obtained earlier and in the present study have shown that SkQ1 is a promising agent for prevention and suppression of AMD.

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Abbreviations

AMD:

age-related macular degeneration

FITC:

fluorescein isothiocyanate

RPE:

retinal pigment epithelium

SkQ1:

10-(6′a-plastoquinonyl)decyltriphenylphosphonium

TFAM:

mitochondrial transcription factor A

VDAC1:

voltage-dependent anionic channel 1

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Acknowledgements

Laser scanning microscopy was performed at the Microscopy Center of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences.

Funding

The study was supported by the Ministry of Science and High Education of the Russian Federation (project no. 14. W03.31.0034, megagrant).

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Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090, Novosibirsk, Russia

    D. V. Telegina, O. S. Kozhevnikova, A. Zh. Fursova & N. G. Kolosova

  2. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Science, 630090, Novosibirsk, Russia

    N. G. Kolosova

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  1. D. V. Telegina
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  2. O. S. Kozhevnikova
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  3. A. Zh. Fursova
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  4. N. G. Kolosova
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Correspondence to N. G. Kolosova.

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Authors declare no conflict of interests. All procedures performed with the animals were in accordance with the ethical standards of the involved Institutions and with the approved legal acts of the Russian Federation and International organizations.

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Telegina, D.V., Kozhevnikova, O.S., Fursova, A.Z. et al. Autophagy as a Target for the Retinoprotective Effects of the Mitochondria-Targeted Antioxidant SkQ1. Biochemistry Moscow 85, 1640–1649 (2020). https://doi.org/10.1134/S0006297920120159

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