Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/140911
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Metabolic Reprogramming of the Retinal Pigment Epithelium by Cytokines Associated with Age-related Macular Degeneration |
Author: | Hansman, D.S. Ma, Y. Thomas, D. Smith, J.R. Casson, R.J. Peet, D. |
Citation: | Bioscience Reports: molecular and cellular biology of the cell surface, 2024; 44(4):BSR20231904.-1-BSR20231904.-20 |
Publisher: | Portland Press, Biochemical Society |
Issue Date: | 2024 |
ISSN: | 0144-8463 1573-4935 |
Statement of Responsibility: | David S. Hansman, Yuefang Ma, Daniel Thomas, Justine R. Smith, Robert J. Casson and Daniel J. Peet |
Abstract: | The complex metabolic relationship between the retinal pigment epithelium (RPE) and photoreceptors is essential for maintaining retinal health. Recent evidence indicates the RPE acts as an adjacent lactate sink, suppressing glycolysis in the epithelium in order to maximize glycolysis in the photoreceptors. Dysregulated metabolism within the RPE has been implicated in the pathogenesis of age-related macular degeneration (AMD), a leading cause of vision loss. 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. |
Keywords: | carbohydrate metabolism cytokines glycolysis inflammation retinal degeneration retinal pigment epithelium |
Description: | Version of Record published: 16 April 2024 |
Rights: | © 2024 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). |
DOI: | 10.1042/BSR20231904 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1099932 |
Published version: | http://dx.doi.org/10.1042/bsr20231904 |
Appears in Collections: | Research Outputs |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
hdl_140911.pdf | Published version | 3.67 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.