ArticleInvestigative ophthalmology & visual science2021
Formation of Lipofuscin-Like Autofluorescent Granules in the Retinal Pigment Epithelium Requires Lysosome Dysfunction.
Article in Investigative ophthalmology & visual science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Cellular accumulation of lipofuscin in the heart: implications in health and disease.Histochemistry and cell biology · 2026Review
- Photoreceptor Vulnerability to Ferroptosis: Membrane Phospholipid Peroxidation, Mitochondrial Homeostasis, and RPE-Photoreceptor Coupling.Current issues in molecular biology · 2026Review
- Loss of REP-1 in retinal pigment epithelial cells leads to impaired phagosome processing and altered lysosomal pathway function.Molecular biology of the cell · 2025Article
- Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration.Antioxidants (Basel, Switzerland) · 2025Review
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Specialised features of melanosomes in health and disease in the retinal pigment epithelium.Frontiers in cell and developmental biology · 2025Review
- Protective effect of zinc against A2E-induced toxicity in ARPE-19 cells: Possible involvement of lysosomal acidification.Heliyon · 2024Article
- RPE melanin and its influence on the progression of AMD.Ageing research reviews · 2024Review
- Impaired cathepsin D in retinal pigment epithelium cells mediates Stargardt disease pathogenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Mitochondrial dysfunction in neurodegenerative disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Classification, location, and intensity of granules in retinal pigment epithelium following sodium iodate injection in rat animal model.Iranian journal of basic medical sciences · 2024Article
- Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina.Antioxidants (Basel, Switzerland) · 2023Review
- The murine retinal pigment epithelium requires peroxisomal β-oxidation to maintain lysosomal function and prevent dedifferentiation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Improved Lipofuscin Models and Quantification of Outer Segment Phagocytosis Capacity in Highly Polarized Human Retinal Pigment Epithelial Cultures.Journal of visualized experiments : JoVE · 2023Article
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
Purpose: We aim to characterize the pathways required for autofluorescent granule (AFG) formation by RPE cells using cultured monolayers. Methods: We fed RPE monolayers in culture with a single pulse of photoreceptor outer segments (POS). After 24 hours the cells started accumulating AFGs that were comparable to lipofuscin in vivo. Using this model, we used a variety of light and electron microscopical techniques, flow cytometry and Western blot to analyze the formation of AFGs. We also generated a mutant RPE line lacking cathepsin D by gene editing. Results: AFGs seem to derive from incompletely digested POS-containing phagosomes and after 3 days are surrounded by a single membrane positive for lysosome markers. We show by various methods that lysosome-phagosome fusion is required for AFG formation, and that impairment of lysosomal pH or catalytic activity, particularly cathepsin D activity, enhances AF accumulation. Conclusions: We conclude that lysosomal dysfunction results in incomplete POS degradation and enhanced AFG accumulation.
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