Cited by 133Retinal Diseases and TreatmentsRetinal Development and DisordersRetinoids in leukemia and cellular processes

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Lipofuscin and N-Retinylidene-N-Retinylethanolamine (A2E) Accumulate in Retinal Pigment Epithelium in Absence of Light Exposure

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Boyer, Nicholas P., Higbee, Daniel, Currin, Mark B., Blakeley, Lorie R., Chen, Chunhe, Ablonczy, Zsolt, Crouch, Rosalie K., Koutalos, Yiannis·2012·Journal of Biological Chemistry

DOI 10.1074/jbc.m111.329235PMC PMC3381188

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Abstract

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 tha…

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“As such, deficiencies in ABCA4 function would lead to an accumulation in N-retinylidene-PE, driving the formation of the precursors of A2E and lipofuscin after photoactivation of rhodopsin.”
BackgroundInfluential
The renewal of photoreceptor cell outer segments
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“Keeping in mind that 10% ofmouse rod outer segments is being phagocytosed daily by theRPE (46), comparison of the amounts ofA2E found in the retina and the accumulated amounts in the RPE would indicate that A2E and probably other lipofuscin precursors be eliminated even in dark-reared animals.”
Background
In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics.
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Authors: Boyer, N. P., Higbee, D., Currin, M. B., Blakeley, L. R., Chen, C., Ablonczy, Z., Crouch, R. K., & Koutalos, Y.
Affiliations: Medical University of South Carolina (US)
Corresponding author: Koutalos, Yiannis
ORCID: Boyer, Nicholas P.
Higbee, Daniel
Koutalos, Yiannis
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2012-06
Volume: 287
Issue: 26
Pages: 22276-22286
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m111.329235
PMC: PMC3381188
OpenAlex: W1984815704
Cited by: 133
References: 59
Citations by year: 2026: 4 · 2025: 9 · 2024: 4 · 2023: 10 · 2022: 7 · 2021: 9 · 2020: 18 · 2019: 2 · 2018: 10 · 2017: 11 · 2016: 6 · 2015: 15 · 2014: 12 · 2013: 10 · 2012: 6
FWCI: 12.86
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 3021 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1c06rr015455-01a1)
National Eye Institute (R01EY019065, EY014850, R01EY014850, EY-014793, R24EY014793, R21EY020661, EY-004939, EY020661, R01EY004939)
National Center for Research Resources (C06 RR-015455)
Topics: Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
Keywords: lipofuscin, A2E, retinal pigment epithelium, rod photoreceptors, light exposure, aging, ABCA4, Stargardt disease, age-related macular degeneration, 11-cis-retinal, all-trans-retinal, rhodopsin regeneration, dark rearing
MeSH terms: Animals, Chromatography, High Pressure Liquid, Color, Light, Lipofuscin, Macular Degeneration, Mice, Inbred C57BL, Microscopy, Fluorescence, Models, Biological, Retina, Retinaldehyde, Retinoids, Rod Cell Outer Segment, ATP-Binding Cassette Transporters, Mice, Retinal Pigment Epithelium

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Lipofuscin and N-Retinylidene-N-Retinylethanolamine (A2E) Accumulate in Retinal Pigment Epithelium in Absence of Light Exposure

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