Research Paper Volume 10, Issue 8 pp 2136—2147
p62 /SQSTM1 coding plasmid prevents age related macular degeneration in a rat model
- 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
Received: August 3, 2018 Accepted: August 21, 2018 Published: August 28, 2018
https://doi.org/10.18632/aging.101537How to Cite
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.