ArticleInvestigative ophthalmology & visual science2008
Restoration of lysosomal pH in RPE cells from cultured human and ABCA4(-/-) mice: pharmacologic approaches and functional recovery.
Article in Investigative ophthalmology & visual science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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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.
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Who cites it
90 citing papers in PubMed, 139 citations in OpenAlex.
- Sustained proton-pump inhibitor exposure and incident age-related macular degeneration: a new-user, population-based cohort study.BMJ open ophthalmology · 2026Observational
- MRC2-mediated collagen internalization is reduced in fibrotic lung fibroblasts and increased upon phenotypic dedifferentiation.JCI insight · 2026Article
- Age-dependent induction of ER stress in retinal pigment epithelium impairs phagocytosis via ADAM17-dependent MERTK shedding.The Journal of biological chemistry · 2026Article
- Monensin and salinomycin exhibit broad-spectrum antiviral activity against enteroviruses by disrupting lysosomal acidification.Archives of virology · 2026Article
- PLGA nanoparticles restore acidic pH and degradative function to compromised lysosomes with Cy3-labeling providing enhanced tracking to lysosomes.American journal of physiology. Cell physiology · 2026Article
- ADORA2A activation restores lysosomal function and photoreceptor outer segment degradation in stressed retinal pigment epithelium.Frontiers in physiology · 2026Article
- Integration of cAMP and TRPV4 Signaling to Optimize Collagen Remodeling for Management of Fibrosis.Cells · 2025Review
- Senescence-associated lysosomal dysfunction impairs cystine deprivation-induced lipid peroxidation and ferroptosis.Nature communications · 2025Article
- Sustained Lysosomal Delivery of Enhanced Cy3-Labeled Acid Nanoparticles Restores Lysosomal pH in Retinal Pigment Epithelial Cells and Astrocytes.bioRxiv : the preprint server for biology · 2025Article
- Bi-allelic variants in three genes encoding distinct subunits of the vesicular AP-5 complex cause hereditary macular dystrophy.American journal of human genetics · 2025Article
- Retinal Pigment Epithelium Under Oxidative Stress: Chaperoning Autophagy and Beyond.International journal of molecular sciences · 2025Review
- The immunotoxin targeting PRLR increases tamoxifen sensitivity and enhances the efficacy of chemotherapy in breast cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- 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
- Article
- CD151 Maintains Endolysosomal Protein Quality to Inhibit Vascular Inflammation.Circulation research · 2024Article
- ABCA4 mediated traumatic proliferative vitreoretinopathy associated with PI3K/Akt signaling pathway.Heliyon · 2024Article
- The Influence of Lysosomal Stress on Dental Pulp Stem Cell-Derived Schwann Cells.Biomolecules · 2024Article
- Impaired Lysosome Reformation in Chloroquine-Treated Retinal Pigment Epithelial Cells.Investigative ophthalmology & visual science · 2023Article
- Oxidative stress induces lysosomal membrane permeabilization and ceramide accumulation in retinal pigment epithelial cells.Disease models & mechanisms · 2023Article
- Endogenous and Exogenous Regulation of Redox Homeostasis in Retinal Pigment Epithelium Cells: An Updated Antioxidant Perspective.International journal of molecular sciences · 2023Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
purposeDegradation of engulfed material is primarily mediated by lysosomal enzymes that function optimally within a narrow range of acidic pH values. RPE cells are responsible for daily degradation of photoreceptor outer segments and are thus particularly susceptible to perturbations in lysosomal pH. The authors hypothesized that elevated lysosomal pH levels could slow enzyme activity and encourage accumulation of partially digested material. Consequently, treatment to lower perturbed lysosomal pH levels may enhance degradative activity.
methodsA high-throughput screening assay was developed to quantify the lysosomal pH of fresh mouse and cultured ARPE-19 cells. The effect of lysosomal pH on outer segment clearance was determined.
resultsLysosomal pH is elevated in RPE cells from ABCA4 knockout mice and in cultured human ARPE-19 cells exposed to N-retinylidene-N-retinylethanolamine (A2E), tamoxifen, or chloroquine. The lysosomal pH of fresh RPE cells from ABCA4(-/-) mice and of chemically compromised RPE cells was reacidified by elevating intracellular cAMP directly. Compromised lysosomal pH was also restored by stimulating A(2A) adenosine or beta-adrenergic receptors, consistent with G(s)-protein coupling of these receptors. Restoring lysosomal pH with these treatments enhanced photoreceptor outer segment clearance, demonstrating functional relevance consistent with an enhancement of degradative enzyme activity.
conclusionsElevation of lysosomal pH in RPE cells interferes with the degradation of outer segments and may contribute to the pathologies associated with A2E. Pharmacologic elevation of cAMP can restore an acid pH and improve degradative function.
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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.