Document Detail


Lipofuscin and N-retinylidene-N-retinylethanolamine (A2E) accumulate in retinal pigment epithelium in absence of light exposure: their origin is 11-cis-retinal.
MedLine Citation:
PMID:  22570475     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The age-dependent accumulation of lipofuscin in the retinal pigment epithelium (RPE) has been associated with the development of retinal diseases, particularly age-related macular degeneration and Stargardt disease. A major component of lipofuscin is the bis-retinoid N-retinylidene-N-retinylethanolamine (A2E). The current model for the formation of A2E requires photoactivation of rhodopsin and subsequent release of all-trans-retinal. To understand the role of light exposure in the accumulation of lipofuscin and A2E, we analyzed RPEs and isolated rod photoreceptors from mice of different ages and strains, reared either in darkness or cyclic light. Lipofuscin levels were determined by fluorescence imaging, whereas A2E levels were quantified by HPLC and UV-visible absorption spectroscopy. The identity of A2E was confirmed by tandem mass spectrometry. Lipofuscin and A2E levels in the RPE increased with age and more so in the Stargardt model Abca4(-/-) than in the wild type strains 129/sv and C57Bl/6. For each strain, the levels of lipofuscin precursor fluorophores in dark-adapted rods and the levels and rates of increase of RPE lipofuscin and A2E were not different between dark-reared and cyclic light-reared animals. Both 11-cis- and all-trans-retinal generated lipofuscin-like fluorophores when added to metabolically compromised rod outer segments; however, it was only 11-cis-retinal that generated such fluorophores when added to metabolically intact rods. The results suggest that lipofuscin originates from the free 11-cis-retinal that is continuously supplied to the rod for rhodopsin regeneration and outer segment renewal. The physiological role of Abca4 may include the translocation of 11-cis-retinal complexes across the disk membrane.
Authors:
Nicholas P Boyer; Daniel Higbee; Mark B Currin; Lorie R Blakeley; Chunhe Chen; Zsolt Ablonczy; Rosalie K Crouch; Yiannis Koutalos
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-08
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-25     Completed Date:  2012-09-20     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  22276-86     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / metabolism
Animals
Chromatography, High Pressure Liquid / methods
Color
Light
Lipofuscin / chemistry*
Macular Degeneration / metabolism
Mice
Mice, Inbred C57BL
Microscopy, Fluorescence / methods
Models, Biological
Retina / metabolism
Retinal Pigment Epithelium / metabolism*
Retinaldehyde / pharmacology
Retinoids / chemistry*
Rod Cell Outer Segment / metabolism
Grant Support
ID/Acronym/Agency:
C06 RR015455/RR/NCRR NIH HHS; EY004939/EY/NEI NIH HHS; EY014793/EY/NEI NIH HHS; EY014850/EY/NEI NIH HHS; EY020661/EY/NEI NIH HHS; R01 EY019065/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/A2-E (N-retinylidene-N-retinylethanolamine); 0/Abca4 protein, mouse; 0/Lipofuscin; 0/Retinoids; 116-31-4/Retinaldehyde
Comments/Corrections

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