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Open AccessArticle

Disruptions of Autophagy in the Rat Retina with Age During the Development of Age-Related-Macular-Degeneration-like Retinopathy

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Pr. Lavrentyeva 10, Novosibirsk 630090, Russia
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Int. J. Mol. Sci. 2019, 20(19), 4804; https://doi.org/10.3390/ijms20194804
Received: 22 August 2019 / Revised: 10 September 2019 / Accepted: 23 September 2019 / Published: 27 September 2019
(This article belongs to the Special Issue Retinal Degeneration: From Pathophysiology to Therapeutic Approaches)
Age-related macular degeneration (AMD) is one of the main causes of vision impairment in the elderly. Autophagy is the process of delivery of cytoplasmic components into lysosomes for cleavage; its age-related malfunction may contribute to AMD. Here we showed that the development of AMD-like retinopathy in OXYS rats is accompanied by retinal transcriptome changes affecting genes involved in autophagy. These genes are associated with kinase activity, immune processes, and FoxO, mTOR, PI3K-AKT, MAPK, AMPK, and neurotrophin pathways at preclinical and manifestation stages, as well as vesicle transport and processes in lysosomes at the progression stage. We demonstrated a reduced response to autophagy modulation (inhibition or induction) in the OXYS retina at age 16 months: expression of genes Atg5, Atg7, Becn1, Nbr1, Map1lc3b, p62, and Gabarapl1 differed between OXYS and Wistar (control) rats. The impaired reactivity of autophagy was confirmed by a decreased number of autophagosomes under the conditions of blocked autophagosome–lysosomal fusion according to immunohistochemical analysis and transmission electron microscopy. Thus, the development of AMD signs occurs against the background of changes in the expression of autophagy-related genes and a decrease in autophagy reactivity: the ability to enhance autophagic flux in response to stress. View Full-Text
Keywords: autophagy; age-related macular degeneration; retina; retinal pigment epithelium; transcriptome; chloroquine; fasting autophagy; age-related macular degeneration; retina; retinal pigment epithelium; transcriptome; chloroquine; fasting
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Kozhevnikova, O.S.; Telegina, D.V.; Tyumentsev, M.A.; Kolosova, N.G. Disruptions of Autophagy in the Rat Retina with Age During the Development of Age-Related-Macular-Degeneration-like Retinopathy. Int. J. Mol. Sci. 2019, 20, 4804.

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