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

Aging
Nataliya G KolosovaAlexander M Shneider

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.

References

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Citations

Jul 25, 2019·Veterinary and Comparative Oncology·Francesca MariottiFranco Maria Venanzi
Sep 26, 2020·Frontiers in Cellular Neuroscience·Jonathan EintrachtMariya Moosajee
Mar 16, 2019·BMC Medical Genomics·Darya V TeleginaOyuna S Kozhevnikova
Jul 28, 2020·International Journal of Molecular Sciences·Darya V TeleginaNataliya G Kolosova
Oct 2, 2019·International Journal of Molecular Sciences·Oyuna S KozhevnikovaNataliya G Kolosova
Feb 12, 2021·International Journal of Molecular Sciences·Janusz BlasiakKai Kaarniranta
Nov 14, 2020·International Journal of Molecular Sciences·Eloise KeelingJ Arjuna Ratnayaka
Mar 12, 2021·Biochemistry. Biokhimii︠a︡·D V TeleginaN G Kolosova

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Methods Mentioned

BETA
transfects

Software Mentioned

Axiovision
ImageJ
Statistica

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