The DOI matches its Crossref record; 56 of the 59 references it cites were found in a registry or an index.
Lipofuscin and N-Retinylidene-N-Retinylethanolamine (A2E) Accumulate in Retinal Pigment Epithelium in Absence of Light Exposure
Open accessAbstract
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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“Immunohistology showed RPE65 to be present in the OS of these cone-like photoreceptors (Figure 6, B-C) (Boyer et al., 2012b).”
From New insights into retinoid metabolism and cycling within the retina (2013) · cites this paper as Boyer et al., 2012b
In the citing paper
“Furthermore, direct addition of 11-cis retinal to rod photoreceptors results in the generation of lipofuscin precursors in the absence of light.”
From New insights into retinoid metabolism and cycling within the retina (2013) · cites this paper as Boyer et al., 2012a
In the citing paper
“While it is clear that retinoids are involved in lipofuscin, recent evidence shows 11-cis retinal itself may be a major source of lipofuscin and A2E (Boyer et al., 2012a).”
From New insights into retinoid metabolism and cycling within the retina (2013) · cites this paper as Boyer et al., 2012a
In the citing paper
“These results are based on the finding that mice raised in the dark have the same levels of lipofuscin and lipofuscin precursors as animals raised in cyclic light.”
From New insights into retinoid metabolism and cycling within the retina (2013) · cites this paper as Boyer et al., 2012a
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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.”
BackgroundInfluentialThe 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.”
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“Mice that lack Abca4 exhibit a large increase in RPE lipofuscin and bis-retinoid, including A2E, accumulation (17, 20, 21).”
BackgroundResultInfluentialRPE lipofuscin and its role in retinal pathobiology
Sparrow, J. R., & Boulton, M. (2005) · Experimental Eye Research · doi:10.1016/j.exer.2005.01.007 · Cited by 644
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Functions, Therapeutic Applications, and Synthesis of Retinoids and Carotenoids
Álvarez, R., Vaz, B., Gronemeyer, H., & de Lera, Á. R. (2014) · Chemical Reviews · doi:10.1021/cr400126u · Cited by 260
Molday, R. S., & Moritz, O. L. (2015) · Journal of Cell Science · doi:10.1242/jcs.175687 · Cited by 235
Senescence in the pathogenesis of age-related macular degeneration
Blasiak, J. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03420-x · Cited by 183
Quantitative Fundus Autofluorescence in Healthy Eyes
Greenberg, J. P., Duncker, T., Woods, R. L., Smith, R. T., Sparrow, J. R., & Delori, F. C. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-12445 · Cited by 168
Lenis, T. L., Hu, J., Ng, S. Y., Jiang, Z., Sarfare, S., Lloyd, M. B., Esposito, N. J., Samuel, W., Jaworski, C., Bok, D., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1802519115 · Cited by 158
Metadata
- 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
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 287
- Issue
- 26
- Pages
- 22276-22286
- ISSN
- 0021-9258 (ISSN-L)
- 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
- 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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