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

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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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BindingDB Entry 50046294: Bicyclic [3.3.0]-Octahydrocyclopenta[c]pyrrolo Antagonists of Retinol Binding Protein 4: Potential Treatment of Atrophic Age-Related Macular Degeneration and Stargardt Disease.
BindingDB (2016) · UC San Diego · doi:10.7270/q20z751f
MicroRNA Expression Signature of Retinal Pigmented Epithelial Cells Associated with the Phenotype of Age-Related Macular Degeneration
Gutierrez, M. A. (2014) · doi:10.33015/dominican.edu/2014.bio.02
Unrepaired Cyclobutane Pyrimidine Dimers Do Not Prevent Proliferation of UV‐B‐irradiated Cultured Human Fibroblasts¶
Courdavault, S., Baudouin, C., Sauvaigo, S., Mouret, S., Candéias, S., Charveron, M., Favier, A., Cadet, J., & Douki, T. (2004) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2004.tb00004.x · Cited by 12

Authors: Finnemann, S. C., Leung, L. W., & Rodriguez-Boulan, E.
Affiliations: Cornell University (US)
Corresponding author: Rodriguez-Boulan, Enrique
ORCID: Finnemann, Silvia C.
Leung, Lawrence W.
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
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: 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
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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The lipofuscin component A2E selectively inhibits phagolysosomal degradation of photoreceptor phospholipid by the retinal pigment epithelium

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