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Cited by 285Retinal Diseases and TreatmentsRetinal Development and DisordersAutophagy in Disease and Therapy

The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.

The lipofuscin component A2E selectively inhibits phagolysosomal degradation of photoreceptor phospholipid by the retinal pigment epithelium

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Finnemann, Silvia C., Leung, Lawrence W., Rodriguez-Boulan, Enrique·2002·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.052025899PMC PMC122611
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Abstract

Daily phagocytosis of spent photoreceptor outer segments is a critical maintenance function performed by the retinal pigment epithelium (RPE) to preserve vision. Aging RPE accumulates lipofuscin, which includes N-retinylidene-N-retinylethanolamine (A2E) as the major autofluorescent component. We studied the effect of physiological levels of A2E in RPE cultures on their ability to phagocytose outer segments. A2E localized to lysosomes in cultured RPE as well as in human RPE in situ. A2E-loaded RPE cells in culture bound and internalized identical numbers of outer segments as control RPE indicating that A2E does not alter early steps of phagocytosis. A2E-loaded RPE degraded outer segment proteins efficiently but, strikingly, failed to completely digest phospholipids within 24 h. Because of the circadian rhythm of RPE phagocytosis in the eye, a delay in lipid degradation would likely result in a build up of undigested material in RPE that could contribute to the development of age-related macular degeneration.

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Research works printed but not linked: 8

  1. B S Winkler, M E Boulton, J D Gottsch, P Sternberg Mol Vis 5, 32 (1999).
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  8. 10.1139/y59-099 · DOI · Paper page

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Metadata

Authors
Finnemann, S. C., Leung, L. W., & Rodriguez-Boulan, E.
Affiliations
Cornell University (US)
Corresponding author
Rodriguez-Boulan, Enrique
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2002-03-19
Volume
99
Issue
6
Pages
3842-3847
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.052025899
PMC
PMC122611
OpenAlex
W2137331743
Cited by
283
References
36
Citations by year
2026: 5 · 2025: 7 · 2024: 8 · 2023: 8 · 2022: 11 · 2021: 14 · 2020: 13 · 2019: 8 · 2018: 11 · 2017: 7 · 2016: 7 · 2015: 21 · 2014: 23 · 2013: 12 · 2012: 18
FWCI
13.13
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Eye Institute (EY08538, R01EY008538)
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords
lipofuscin, A2E, retinal pigment epithelium, photoreceptor outer segment phagocytosis, phospholipid degradation, lysosomes, age-related macular degeneration, autofluorescence
MeSH terms
Cell Line, Fluorescent Antibody Technique, Humans, Lipofuscin, Liposomes, Lysosomes, Macular Degeneration, Middle Aged, Phagocytosis, Phagosomes, Phosphatidylcholines, Phospholipids, Photoreceptor Cells, Pigment Epithelium of Eye, Pyridinium Compounds, Retinoids, Fluorescein-5-isothiocyanate

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