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Research Paper|Volume 10, Issue 8|pp 2136—2147

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

Nataliya G. Kolosova1, Oyuna S. Kozhevnikova1, Darya V. Telegina1, Anzhela Zh. Fursova1,2, Natalia A. Stefanova1, Natalia A. Muraleva1, Franco Venanzi4, Michael Y. Sherman5, Sergey I. Kolesnikov7,8,9, Albert A. Sufianov6,11, Vladimir L. Gabai3,10, Alexander M. Shneider3,5,6
  • 1Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia
  • 2Novosibirsk State Regional Clinical Hospital, Novosibirsk, Russia
  • 3CureLab Oncology, Inc, Deadham, MA 02492, USA
  • 4School of Biosciences, University of Camerino, Camerino, Italy
  • 5Department of Molecular Biology, Ariel University, Ariel, Israel
  • 6Sechenov First Moscow State Medical University, Moscow, Russia
  • 7Russian Academy of Sciences, Moscow, Russia
  • 8Lomonosov Moscow State University, Moscow, Russia
  • 9Research Center of Family Health and Reproduction Problems, Irkutsk, Russia
  • 10Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA
  • 11Federal Center of Neurosurgery, Tyumen, Russia

* * Equal contribution

Received: August 3, 2018Accepted: August 21, 2018Published: August 28, 2018
https://doi.org/10.18632/aging.101537

Copyright: © 2018 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.