P62 /SQSTM1 Coding Plasmid Prevents Age Related Macular Degeneration in a Rat Model

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2018 Aug 29

PMID 30153656

Citations 17

Authors

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

Affiliations

Soon will be listed here.

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.

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