Evidence map›Paper›PMID 40234500›Full record

ArticleScientific reports2025

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.

David S Hansman, Kelly Lim, Daniel Thomas, Robert J Casson, Daniel J Peet

Abstract readComparative Study
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

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.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

5 authors.

David S HansmanSchool of Biological Sciences, University of Adelaide, Adelaide, SA, Australia.
Kelly LimSouth Australian Health and Medical Research Institute, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
Daniel ThomasSouth Australian Health and Medical Research Institute, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
Robert J CassonDiscipline of Ophthalmology and Visual Science, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
Daniel J PeetSchool of Biological Sciences, University of Adelaide, Adelaide, SA, Australia. daniel.peet@adelaide.edu.au.

Funding

National Health and Medical Research Council of Australia 1099932The Leukemia Foundation 6619-21
6 · The paper itself

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.

Indexed as

CytokinesMacular DegenerationMetabolomeRetinal Pigment EpitheliumAnimalsCell LineHumansMetabolomicsRatsCytokinesAge-related macular degenerationCytokinesMetabolic ecosystemMetabolismRetina inflammationRetinal pigment epithelium

Identifiers

PMID40234500
PMCPMC12000464

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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.