p62 /SQSTM1 coding plasmid prevents age related macular degeneration in a rat model

Nataliya G. Kolosova; Oyuna S. Kozhevnikova; Darya V. Telegina; Anzhela Zh. Fursova; Natalia A. Stefanova; Natalia A. Muraleva; Franco Venanzi; Michael Y. Sherman; Sergey I. Kolesnikov; Albert A. Sufianov; Vladimir L. Gabai; Alexander M. Shneider

doi:doi:10.18632/aging.101537

Research Paper Volume 10, Issue 8 pp 2136—2147

p62 /SQSTM1 coding plasmid prevents age related macular degeneration in a rat model

Nataliya G. Kolosova^{1,

,}, Oyuna S. Kozhevnikova^{1,

,}, Darya V. Telegina^1,, Anzhela Zh. Fursova^1,2,, Natalia A. Stefanova^1,, Natalia A. Muraleva^1,, Franco Venanzi^4,, Michael Y. Sherman^5,, Sergey I. Kolesnikov^7,8,9,, Albert A. Sufianov^6,11,, Vladimir L. Gabai^3,10,, Alexander M. Shneider^3,5,6,,

¹ Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia
² Novosibirsk State Regional Clinical Hospital, Novosibirsk, Russia
³ CureLab Oncology, Inc, Deadham, MA 02492, USA
⁴ School of Biosciences, University of Camerino, Camerino, Italy
⁵ Department of Molecular Biology, Ariel University, Ariel, Israel
⁶ Sechenov First Moscow State Medical University, Moscow, Russia
⁷ Russian Academy of Sciences, Moscow, Russia
⁸ Lomonosov Moscow State University, Moscow, Russia
⁹ Research Center of Family Health and Reproduction Problems, Irkutsk, Russia
¹⁰ Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA
¹¹ Federal Center of Neurosurgery, Tyumen, Russia

* Equal contribution

Received: August 3, 2018 Accepted: August 21, 2018 Published: August 28, 2018

https://doi.org/10.18632/aging.101537
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Kolosova NG, Kozhevnikova OS, Telegina DV, Fursova AZ, Stefanova NA, Muraleva NA, Venanzi F, Sherman MY, Kolesnikov SI, Sufianov AA, Gabai VL, Shneider AM, . p62 /SQSTM1 coding plasmid prevents age related macular degeneration in a rat model. Aging (Albany NY). 2018; 10:2136-2147. https://doi.org/10.18632/aging.101537

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Provider: 
        TY  - JOUR
        AU  - Kolosova, Nataliya G. 
        AU  - Kozhevnikova, Oyuna S. 
        AU  - Telegina, Darya V. 
        AU  - Fursova, Anzhela Zh. 
        AU  - Stefanova, Natalia A. 
        AU  - Muraleva, Natalia A. 
        AU  - Venanzi, Franco 
        AU  - Sherman, Michael Y. 
        AU  - Kolesnikov, Sergey I. 
        AU  - Sufianov, Albert A. 
        AU  - Gabai, Vladimir L. 
        AU  - Shneider, Alexander M. 
        TI  - p62 /SQSTM1 coding plasmid prevents age related macular degeneration in a rat model
        JO  - 
        JA  - Aging (Albany NY)
        VL  - 10
        IS  - 8
        PB  - 
        SN  - 
        UR  - https://doi.org/10.18632/aging.101537
        DO  - 10.18632/aging.101537
        SP  - 2136
        EP  - 2147
        PY  - 
        AB  - P62/SQSTM1, a multi-domain protein that regulates inflammation, apoptosis, and autophagy, has been linked to age-related pathologies. For example, previously we demonstrated that administration of p62/SQSTM1-encoding plasmid reduced chronic inflammation and alleviated osteoporosis and metabolic syndrome in animal models. Herein, we built upon these findings to investigate effect of the p62-encoding plasmid on an age-related macular degeneration (AMD), a progressive neurodegenerative ocular disease, using spontaneous retinopathy in senescence-accelerated OXYS rats as a model. Overall, the p62DNA decreased the incidence and severity of retinopathy. In retinal pigment epithelium (RPE), p62DNA administration slowed down development of the destructive alterations of RPE cells, including loss of regular hexagonal shape, hypertrophy, and multinucleation. In neuroretina, p62DNA prevented gliosis, retinal thinning, and significantly inhibited microglia/macrophages migration to the outer retina, prohibiting their subretinal accumulation. Taken together, our results suggest that the p62DNA has a strong retinoprotective effect in AMD.
        ER  -

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Copyright: Kolosova et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

P62/SQSTM1, a multi-domain protein that regulates inflammation, apoptosis, and autophagy, has been linked to age-related pathologies. For example, previously we demonstrated that administration of p62/SQSTM1-encoding plasmid reduced chronic inflammation and alleviated osteoporosis and metabolic syndrome in animal models. Herein, we built upon these findings to investigate effect of the p62-encoding plasmid on an age-related macular degeneration (AMD), a progressive neurodegenerative ocular disease, using spontaneous retinopathy in senescence-accelerated OXYS rats as a model. Overall, the p62DNA decreased the incidence and severity of retinopathy. In retinal pigment epithelium (RPE), p62DNA administration slowed down development of the destructive alterations of RPE cells, including loss of regular hexagonal shape, hypertrophy, and multinucleation. In neuroretina, p62DNA prevented gliosis, retinal thinning, and significantly inhibited microglia/macrophages migration to the outer retina, prohibiting their subretinal accumulation. Taken together, our results suggest that the p62DNA has a strong retinoprotective effect in AMD.

Research Paper Volume 10, Issue 8 pp 2136—2147

p62 /SQSTM1 coding plasmid prevents age related macular degeneration in a rat model

Received: August 3, 2018 Accepted: August 21, 2018 Published: August 28, 2018

Abstract

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