Liraglutide Attenuates FFA-Induced Retinal Pigment Epithelium Dysfunction via AMPK Activation and Lipid Homeostasis Regulation in ARPE-19 Cells

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3704 - 3704

Published: April 14, 2025

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly, and it characterized by oxidative stress, lipid dysregulation, dysfunction retinal pigment epithelium (RPE). A hallmark AMD presence drusen, extracellular deposits rich lipids, proteins, cellular debris, which are secreted RPE. These impair RPE function, promote chronic inflammation, accelerate disease progression. Despite advancements understanding pathogenesis, therapeutic strategies targeting dysregulation damage cells remain limited. This study evaluated effects liraglutide, glucagon-like peptide-1 receptor agonist (GLP-1RA), on free fatty acid (FFA)-induced ARPE-19 cells, widely used vitro model dysfunction. FFA treatment induced droplet accumulation, epithelial–mesenchymal transition (EMT), processes implicated Liraglutide significantly reduced mitigated suppressed EMT, as demonstrated high-content imaging, immunocytochemistry, molecular assays. Mechanistic analyses revealed that liraglutide activates AMP-activated protein kinase (AMPK), enhancing lipophagy restoring homeostasis. Furthermore, influenced exosome secretion, altering paracrine signaling reducing EMT markers neighboring cells. findings underscore liraglutide’s potential to address critical mechanisms underlying including EMT. provides foundational evidence supporting development GLP-1 agonists targeted therapies for AMD.

Language: Английский

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The Critical Role of GLP-1 Signaling Pathways in the Pathology of Parkinson's Disease and Diabetes

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: unknown, P. 155985 - 155985

Published: April 1, 2025

Language: Английский

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GLP-1-based therapies for diabetes, obesity and beyond

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Language: Английский

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