Distinct metabolome and flux responses in the retinal pigment epithelium to cytokines associated with age-related macular degeneration: comparison of ARPE-19 cells and eyecups
Abstract Age-related macular degeneration (AMD) is associated with chronic inflammation of the retinal pigment epithelium (RPE) and elevated cytokines including TNFα, TGF-β, IL-6, and IL-1β. As a metabolic intermediary supporting aerobic glycolysis in the adjacent photoreceptors, the RPE’s metabolic...
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Nature Portfolio
2025-04-01
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| Online Access: | https://doi.org/10.1038/s41598-025-93882-w |
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| author | David S. Hansman Kelly Lim Daniel Thomas Robert J. Casson Daniel J. Peet |
| author_facet | David S. Hansman Kelly Lim Daniel Thomas Robert J. Casson Daniel J. Peet |
| author_sort | David S. Hansman |
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| description | Abstract Age-related macular degeneration (AMD) is associated with chronic inflammation of the retinal pigment epithelium (RPE) and elevated cytokines including TNFα, TGF-β, IL-6, and IL-1β. As a metabolic intermediary supporting aerobic glycolysis in the adjacent photoreceptors, the RPE’s metabolic responses to inflammation and the optimal methods to study cytokine-driven metabolic programming remain unclear. We performed a rigorous comparison of ARPE-19 cells and rat eyecup metabolomes, revealing key distinctions. Rat eyecups exhibit higher levels of lactate and palmitate but depleted glutathione and high-energy nucleotides. Conversely, ARPE-19 cells are enriched with high-energy currency metabolites and the membrane phospholipid precursors phosphocholine and inositol. Both models showed contrasting responses to individual cytokines: ARPE-19 cells were more sensitive to TNFα, while eyecups responded more strongly to TGF-β2. Notably, a combined cytokine cocktail elicited stronger metabolic effects on ARPE-19 cells, more potently impacting both metabolite abundance (41 vs. 29) and glucose carbon flux (29 vs. 5), and influencing key RPE metabolites such as alanine, glycine, aspartate, proline, citrate, α-ketoglutarate, and palmitate. Overall, these findings position ARPE-19 cells as a more responsive platform for studying inflammatory cytokine effects on RPE metabolism and reveal critical RPE metabolites which may be linked with AMD pathogenesis. |
| format | Article |
| id | doaj-art-e55c2c4dfd9d478b888dc57db59fb8d6 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-e55c2c4dfd9d478b888dc57db59fb8d62025-08-20T02:17:54ZengNature PortfolioScientific Reports2045-23222025-04-0115111710.1038/s41598-025-93882-wDistinct metabolome and flux responses in the retinal pigment epithelium to cytokines associated with age-related macular degeneration: comparison of ARPE-19 cells and eyecupsDavid S. Hansman0Kelly Lim1Daniel Thomas2Robert J. Casson3Daniel J. Peet4School of Biological Sciences, University of AdelaideSouth Australian Health and Medical Research Institute, Adelaide Medical School, University of AdelaideSouth Australian Health and Medical Research Institute, Adelaide Medical School, University of AdelaideDiscipline of Ophthalmology and Visual Science, Adelaide Medical School, University of AdelaideSchool of Biological Sciences, University of AdelaideAbstract Age-related macular degeneration (AMD) is associated with chronic inflammation of the retinal pigment epithelium (RPE) and elevated cytokines including TNFα, TGF-β, IL-6, and IL-1β. As a metabolic intermediary supporting aerobic glycolysis in the adjacent photoreceptors, the RPE’s metabolic responses to inflammation and the optimal methods to study cytokine-driven metabolic programming remain unclear. We performed a rigorous comparison of ARPE-19 cells and rat eyecup metabolomes, revealing key distinctions. Rat eyecups exhibit higher levels of lactate and palmitate but depleted glutathione and high-energy nucleotides. Conversely, ARPE-19 cells are enriched with high-energy currency metabolites and the membrane phospholipid precursors phosphocholine and inositol. Both models showed contrasting responses to individual cytokines: ARPE-19 cells were more sensitive to TNFα, while eyecups responded more strongly to TGF-β2. Notably, a combined cytokine cocktail elicited stronger metabolic effects on ARPE-19 cells, more potently impacting both metabolite abundance (41 vs. 29) and glucose carbon flux (29 vs. 5), and influencing key RPE metabolites such as alanine, glycine, aspartate, proline, citrate, α-ketoglutarate, and palmitate. Overall, these findings position ARPE-19 cells as a more responsive platform for studying inflammatory cytokine effects on RPE metabolism and reveal critical RPE metabolites which may be linked with AMD pathogenesis.https://doi.org/10.1038/s41598-025-93882-wAge-related macular degenerationRetinal pigment epitheliumMetabolismRetina inflammationCytokinesMetabolic ecosystem |
| spellingShingle | David S. Hansman Kelly Lim Daniel Thomas Robert J. Casson Daniel J. Peet Distinct metabolome and flux responses in the retinal pigment epithelium to cytokines associated with age-related macular degeneration: comparison of ARPE-19 cells and eyecups Scientific Reports Age-related macular degeneration Retinal pigment epithelium Metabolism Retina inflammation Cytokines Metabolic ecosystem |
| title | Distinct metabolome and flux responses in the retinal pigment epithelium to cytokines associated with age-related macular degeneration: comparison of ARPE-19 cells and eyecups |
| title_full | Distinct metabolome and flux responses in the retinal pigment epithelium to cytokines associated with age-related macular degeneration: comparison of ARPE-19 cells and eyecups |
| title_fullStr | Distinct metabolome and flux responses in the retinal pigment epithelium to cytokines associated with age-related macular degeneration: comparison of ARPE-19 cells and eyecups |
| title_full_unstemmed | Distinct metabolome and flux responses in the retinal pigment epithelium to cytokines associated with age-related macular degeneration: comparison of ARPE-19 cells and eyecups |
| title_short | Distinct metabolome and flux responses in the retinal pigment epithelium to cytokines associated with age-related macular degeneration: comparison of ARPE-19 cells and eyecups |
| title_sort | distinct metabolome and flux responses in the retinal pigment epithelium to cytokines associated with age related macular degeneration comparison of arpe 19 cells and eyecups |
| topic | Age-related macular degeneration Retinal pigment epithelium Metabolism Retina inflammation Cytokines Metabolic ecosystem |
| url | https://doi.org/10.1038/s41598-025-93882-w |
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