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

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dc.contributor.authorHansman, D.S.
dc.contributor.authorLim, K.
dc.contributor.authorThomas, D.
dc.contributor.authorCasson, R.J.
dc.contributor.authorPeet, D.J.
dc.date.issued2025
dc.description.abstractAge-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.
dc.description.statementofresponsibilityDavid S. Hansman, Kelly Lim, Daniel Thomas, Robert J. Casson, Daniel J. Peet
dc.identifier.citationScientific Reports, 2025; 15(1):13012-1-13012-17
dc.identifier.doi10.1038/s41598-025-93882-w
dc.identifier.issn2045-2322
dc.identifier.issn2045-2322
dc.identifier.orcidLim, K. [0000-0003-4606-7588]
dc.identifier.orcidCasson, R.J. [0000-0003-2822-4076]
dc.identifier.orcidPeet, D.J. [0000-0002-6085-8936]
dc.identifier.urihttps://hdl.handle.net/2440/147026
dc.language.isoen
dc.publisherNature Portfolio
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1099932
dc.relation.grantNHMRC
dc.rights© The Author(s) 2025. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommo ns.org/licenses/by-nc-nd/4.0/.
dc.source.urihttps://doi.org/10.1038/s41598-025-93882-w
dc.subjectage-related macular degeneration; retinal pigment epithelium; metabolism; retina inflammation; cytokines; metabolic ecosystem
dc.subject.meshCell Line
dc.titleDistinct metabolome and flux responses in the retinal pigment epithelium to cytokines associated with age-related macular degeneration: comparison of ARPE-19 cells and eyecups
dc.typeJournal article
pubs.publication-statusPublished

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