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

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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 agerelated 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.

Original languageEnglish
Pages (from-to)2136-2147
Number of pages12
JournalAging
Volume10
Issue number8
DOIs
StatePublished - 1 Aug 2018

Keywords

  • Age-related macular degeneration
  • Aging
  • Gliosis
  • Inflammation
  • OXYS rats
  • Retina
  • p62/SQSTM1

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