Metabolic Reprogramming of the Retinal Pigment Epithelium by Cytokines Associated with Age-related Macular Degeneration

In this study, we investigate the effects of four cytokines associated with AMD, TNFα, TGF-β2, IL-6, and IL-1β, as well as a cocktail containing all four cytokines, on RPE metabolism using ARPE-19 cells, primary human RPE cells, and ex vivo rat eyecups. Strikingly, we found cytokine-specific changes in numerous metabolic markers including lactate production, glucose consumption, extracellular acidification rate, and oxygen consumption rate accompanied by increases in total mitochondrial volume and ATP production. Together, all four cytokines, could potently override the constitutive suppression of glycolysis in the RPE, through a mechanism independent by PI3K/AKT, MEK/ERK, or NF-κB. Finally, we observed changes in glycolytic gene expression with cytokine treatment, including in lactate dehydrogenase subunit and glucose transporter expression. Our findings provide new insights into the metabolic changes in the RPE under inflammatory conditions and highlight potential therapeutic targets for AMD.PMID:38567515 | DOI:10.1042/BSR20231904
Source: Bioscience Reports - Category: Biomedical Science Authors: Source Type: research