Document Detail


Circadian and noncircadian modulation of autophagy in photoreceptors and retinal pigment epithelium.
MedLine Citation:
PMID:  24781939     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Autophagy in photoreceptors and the RPE promotes homeostasis and survival. The purpose of this study is to determine the daily pattern of changes in autophagy and factors contributing to its regulation in the outer retina.
METHODS: Levels of autophagy markers in the retina and RPE were evaluated over a 24-hour period. To assess the role of phagocytosis in stimulating autophagy in the RPE, cultured RPE-J cells were incubated with isolated photoreceptor outer segments and levels of autophagy markers were measured. Electron microscopy was performed on retina sections and RPE-J cells to assess formation of double-membraned vesicles consistent with autophagosomes.
RESULTS: In wild-type C57BL/6 mice maintained under normal cycling light conditions, autophagy in photoreceptor cells and the RPE exhibited a bimodal pattern of activation. In photoreceptors, shifts between light and dark evoked a sharp decrease in autophagy that was followed by a time-dependent increase. In photoreceptors, translocation of transducin and arrestin from the outer to inner segment appeared to contribute to the light-dependent upregulation of autophagy. In contrast, the cyclic variations in RPE autophagy were independent of lighting conditions, and are triggered, at least in part, by ingestion of outer segments.
CONCLUSIONS: Activation of autophagy in the outer retina exhibits a bimodal pattern that correlates with shifts in transduction proteins within the photoreceptor and by circadian ingestion of outer segments in the RPE. These dynamic shifts suggest a critical role for this pathway in maintaining homeostasis, with further study needed to define the mechanisms underlying the regulation of this phenomenon.
Authors:
Jingyu Yao; Lin Jia; Shameka J Shelby; Anna M Ganios; Kecia Feathers; Debra A Thompson; David N Zacks
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2014-04-29
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  55     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-05-28     Completed Date:  2014-07-22     Revised Date:  2014-11-04    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3237-46     Citation Subset:  IM    
Copyright Information:
Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
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MeSH Terms
Descriptor/Qualifier:
Animals
Autophagy / physiology*
Cells, Cultured
Circadian Rhythm / physiology*
Homeostasis / physiology*
Mice
Mice, Inbred C57BL
Microscopy, Electron
Photoreceptor Cells, Vertebrate / metabolism,  ultrastructure*
Retinal Pigment Epithelium / metabolism,  ultrastructure*
Signal Transduction
Grant Support
ID/Acronym/Agency:
P30 DK020572/DK/NIDDK NIH HHS; R01 EY020823/EY/NEI NIH HHS; R01-EY-020823/EY/NEI NIH HHS; T32 EY013934/EY/NEI NIH HHS
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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