ArticleInvestigative ophthalmology & visual science2019
Highly Differentiated Human Fetal RPE Cultures Are Resistant to the Accumulation and Toxicity of Lipofuscin-Like Material.
Article in Investigative ophthalmology & visual science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Bisretinoid lipofuscin, fundus autofluorescence and retinal disease.Progress in retinal and eye research · 2025Review
- Age-Related Macular Degeneration: Cellular and Molecular Signaling Mechanisms.International journal of molecular sciences · 2025Review
- Oral 8-aminoguanine against age-related retinal degeneration.Communications biology · 2025Article
- Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bodies and Relevance of HMGCS2 to Health and Disease.Biomolecules · 2025Review
- A cell culture system for RPE hypoxia, a physiologic stressor relevant to AMD deposit formation.Eye (London, England) · 2025Article
- Retinal pigment epithelium-specific ablation of GPx4 in adult mice recapitulates key features of geographic atrophy in age-related macular degeneration.Cell death & disease · 2024Article
- Tissue Engineering of Outer Blood Retina Barrier for Therapeutic Development.Current opinion in biomedical engineering · 2024Article
- Reassessing retinal pigment epithelial ketogenesis: Enzymatic assays for ketone body levels provide inaccurate results.Experimental eye research · 2024Article
- Age-Related RPE changes in Wildtype C57BL/6J Mice between 2 and 32 Months.bioRxiv : the preprint server for biology · 2024Article
- Lipofuscin, Its Origin, Properties, and Contribution to Retinal Fluorescence as a Potential Biomarker of Oxidative Damage to the Retina.Antioxidants (Basel, Switzerland) · 2023Review
- Medium Depth Influences O2 Availability and Metabolism in Human RPE Cultures.Investigative ophthalmology & visual science · 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
- Bisretinoids of the Retina: Photo-Oxidation, Iron-Catalyzed Oxidation, and Disease Consequences.Antioxidants (Basel, Switzerland) · 2021Review
- Stages of Drusen-Associated Atrophy in Age-Related Macular Degeneration Visible via Histologically Validated Fundus Autofluorescence.Ophthalmology. Retina · 2021Article
- Regression of drusen or vitelliform material heralding geographic atrophy: correlation between clinical observations and basic science.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2021Article
- Age-related macular degeneration.Nature reviews. Disease primers · 2021Review
- Article
- Sodium iodate induces ferroptosis in human retinal pigment epithelium ARPE-19 cells.Cell death & disease · 2021Article
- Quantitative Fundus Autofluorescence in Systemic Chloroquine/Hydroxychloroquine Therapy.Translational vision science & technology · 2020Article
- Age, lipofuscin and melanin oxidation affect fundus near-infrared autofluorescence.EBioMedicine · 2019Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Purpose: The accumulation of undigestible autofluorescent material (UAM), termed lipofuscin in vivo, is a hallmark of aged RPE. Lipofuscin derives, in part, from the incomplete degradation of phagocytized photoreceptor outer segments (OS). Whether this accumulated waste is toxic is unclear. We therefore investigated the effects of UAM in highly differentiated human fetal RPE (hfRPE) cultures. Methods: Unmodified and photo-oxidized OS were fed daily to confluent cultures of ARPE-19 RPE or hfRPE. The emission spectrum, composition, and morphology of resulting UAM were measured and compared to in vivo lipofuscin. Effects of UAM on multiple RPE phenotypes were assessed. Results: Compared to ARPE-19, hfRPE were markedly less susceptible to UAM buildup. Accumulated UAM in hfRPE initially resembled the morphology of lipofuscin from AMD eyes, but compacted and shifted spectrum over time to resemble lipofuscin from healthy aged human RPE. UAM accumulation mildly reduced transepithelial electrical resistance, ketogenesis, certain RPE differentiation markers, and phagocytosis efficiency, while inducing senescence and rare, focal pockets of epithelial-mesenchymal transition. However, it had no effects on mitochondrial oxygen consumption rate, certain other RPE differentiation markers, secretion of drusen components or polarity markers, nor cell death. Conclusions: hfRPE demonstrates a remarkable resistance to UAM accumulation, suggesting mechanisms for efficient OS processing that may be lost in other RPE culture models. Furthermore, while UAM alters hfRPE phenotype, the effects are modest, consistent with conflicting reports in the literature on the toxicity of lipofuscin. Our results suggest that healthy RPE may adequately adapt to and tolerate lipofuscin accumulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.