The lipofuscin component A2E selectively inhibits phagolysosomal degradation of photoreceptor phospholipid by the retinal pigment epithelium
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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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RPE cell lines lack some RPE polarity features, have reduced expression of a large proportion of RPE signature genes, and typically exhibit much slower phagosome degradation kinetics than primary RPE cultures.
“cultures of RPE cell lines, which have been reported to lack some RPE polarity features (Lehmann et al., 2014), have reduced expression of a large proportion of “RPE signature genes” (Strunnikova et al., 2010), and typically exhibit kinetics of phagosome degradation that is much slower than that found in vivo and in primary RPE cultures (Finnemann et al., 2002; Mazzoni et al., 2014).”
From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Finnemann et al., 2002
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- Authors
- Finnemann, S. C., Leung, L. W., & Rodriguez-Boulan, E.
- Affiliations
- Cornell University (US)
- Corresponding author
- Rodriguez-Boulan, Enrique
- 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
- 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
- bronze
- doi.org
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Epidemiology › 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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