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Retinoprotective Effect of SkQ1, Visomitin Eye Drops, Is Associated with Suppression of P38 MAPK and ERK1/2 Signaling Pathways Activity

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Abstract

Visomitin eye drops are the first and, so far, the only drug based on SkQ1 – the mitochondria-targeted antioxidant 10-(6′-plastoquinonyl) decyltriphenylphosphonium, developed in the laboratories of Moscow State University under the leadership of Academician V. P. Skulachev. SkQ1 is considered as a potential tool to combat the aging program. We have previously shown that it is able to prevent and/or suppress development of all manifestations of accelerated senescence in OXYS rats, including retinopathy, similar to the age-related macular degeneration (AMD). Here, we assessed the effect of Visomitin instillations on progression of the AMD-like pathology and p38 MAPK and ERK1/2 activity in the OXYS rat retina (from the age of 9 to 12 months). Wistar and OXYS rats treated with placebo (composition identical to Visomitin with the exception of SkQ1) were used as controls. Ophthalmological examination showed that in the OXYS rats receiving placebo, retinopathy progressed and severity of clinical manifestations did not differ from the intact OXYS rats. Visomitin suppressed progression of the AMD-like pathology in the OXYS rats and significantly improved structural and functional parameters of the retinal pigment epithelium cells and state of microcirculation in the choroid, which, presumably, contributed to preservation of photoreceptors, associative and ganglion neurons. It was found that the activity of p38 MAPK and ERK1/2 in the retina of 12-month-old OXYS rats is higher than that of the Wistar rats of the same age, as indicated by the increased content of phosphorylated forms of p38 MAPK and ERK1/2 and their target protein tau (at position T181 and S396). Visomitin decreased phosphorylation of p38 MAPK, ERK1/2, and tau indicating suppression of activity of these MAPK signaling cascades. Thus, Visomitin eye drops are able to suppress progression of the AMD-like pathology in the OXYS rats and their effect is associated with the decrease in activity of the MAPK signaling cascades.

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Abbreviations

Aβ:

amyloid beta

AMD:

age-related macular degeneration

ERK1/2:

extracellular signal-regulated kinase 1 and 2

MAPK:

mitogen-activated protein kinases

mTOR:

mammalian target of rapamycin

RPE:

retinal pigment epithelium

SkQ1:

10-(6′-plastoquinonyl)decyltriphenylphosphonium

VEGF:

vascular endothelial growth factor

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Funding

This work was financially supported by the Russian Foundation of Basic Research, grant no. 22-25-00224.

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Authors and Affiliations

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

    Natalia A. Muraleva, Anzhella Zh. Fursova & Nataliya G. Kolosova

  2. Department of Histology, Embryology and Cytology, Siberian State Medical University, 634055, Tomsk, Russia

    Anna A. Zhdankina

  3. Department of Ophthalmology, Novosibirsk State Medical University, 630091, Novosibirsk, Russia

    Anzhella Zh. Fursova

  4. State Novosibirsk Regional Clinical Hospital, 630087, Novosibirsk, Russia

    Anzhella Zh. Fursova

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  1. Natalia A. Muraleva
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  2. Anna A. Zhdankina
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  3. Anzhella Zh. Fursova
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  4. Nataliya G. Kolosova
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Contributions

N.A.M. concept of the study, conducting experiments, discussion of the results of the study; A.Zh.F. ophthalmological examination of animals; A.A.Zh. histomorphometric analysis of retina samples; A.Zh.F., A.A.Zh., N.A.M., and N.G.K. preparation and editing of the paper text.

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Correspondence to Natalia A. Muraleva.

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Muraleva, N.A., Zhdankina, A.A., Fursova, A.Z. et al. Retinoprotective Effect of SkQ1, Visomitin Eye Drops, Is Associated with Suppression of P38 MAPK and ERK1/2 Signaling Pathways Activity. Biochemistry Moscow 89, 201–211 (2024). https://doi.org/10.1134/S0006297924020020

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