Integrated analysis of transcriptomics and metabolomics reveals the mechanisms underlying green tea intervention in age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is a degenerative disease that severely impairs vision, often accompanied by oxidative stress damage, cellular apoptosis, and inflammatory responses in the retina. Green tea, which is rich in polyphenols, typically exhibits strong antioxidant, anti-apoptotic, and anti-inflammatory properties. In this study, an AMD rat model was induced through a combination of intense light exposure and intraperitoneal injection of sodium iodate. An integrated systems biology approach, combining metabolomics and transcriptomics analysis, was employed to investigate the pharmacological basis of green tea extract (GTE) intervention, elucidate key mechanisms of action, and screen for potential biomarkers. The results indicated that GTE significantly improved oxidative stress damage and inflammatory responses in the retina of AMD rats. Additionally, GTE inhibited retinal cell apoptosis by regulating the expression of caspase-3 protein. Integrated metabolomics and transcriptomics analyses revealed that GTE activates Glycerophospholipid metabolism, Ether lipid metabolism, Retinol metabolism, Arachidonic acid metabolism, and Vascular smooth muscle contraction signaling pathways in the retina of AMD rats. This activation was achieved through the modulation of gene expressions such as Pla2g3, Mboat1, and Awat2, influencing the levels of retinol, prostaglandin F2α, and multiple phospholipid metabolites in the retina. qRT-PCR experiments confirmed that GTE can regulate the expression levels of several key genes involved in inflammatory responses, phospholipid metabolism, and retinol metabolism, thereby enhancing its therapeutic activity against AMD. In summary, these findings confirm the substantial therapeutic potential of green tea in the treatment of AMD, providing a foundation for clinical applications and drug development.