
BMC Biology, Journal Year: 2025, Volume and Issue: 23(1)
Published: April 12, 2025
Age-related macular degeneration (AMD) is a leading cause of blindness, characterized by retinal pigment epithelium (RPE) dysfunction, extracellular deposit formation, and disrupted lipid metabolism. Understanding the molecular changes underlying AMD essential for identifying diagnostic markers therapeutic targets. This multiomic study employed primary RPE culture model to investigate age-related associated with AMD. Over 25 weeks, cells exhibited phenotypic deterioration, including depigmentation, cell shape deformation, barrier integrity loss, accompanied formation. Transcriptomic analysis revealed dysregulation genes involved in metabolism, pathways cholesterol transport, glycerophospholipids, ceramide biosynthesis. Metabolomic profiling further identified significant glycerophospholipid sphingolipid highlighting decline phospholipid species accumulation. Serum patients altered levels 18 lipids cultures. Four showed differences compared controls: GlcCer(d16:1/18:0) (1.23-fold increase, adj. p value < 0.001), PE(19:1(9Z)/22:2(13Z,16Z)) (0.34-fold decrease, PE(15:0/20:3(5Z,8Z,11Z)) (0.66-fold 0.05), PC(22:2(13Z,16Z)/13:0) (0.71-fold 0.05). These findings underscore systemic nature translational relevance model. highlights role metabolism pathogenesis. The consistent lipidomic alterations observed cultures patient serum reinforce their potential as biomarkers disease progression provide robust framework understanding AMD-associated impact.
Language: Английский