| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Álvarez-Barrios, Ana Álvarez, Lydia Sáenz de Santa María, Pilar García, Montserrat Álvarez-Buylla, Jorge R. Pereiro, Rosario González-Iglesias, Héctor |
| Abstract | Background 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 is essential for identifying diagnostic markers and therapeutic targets. Results This multiomic study employed a primary RPE culture model to investigate age-related changes associated with AMD. Over 25 weeks, RPE cells exhibited phenotypic deterioration, including depigmentation, cell shape deformation, and barrier integrity loss, accompanied by extracellular deposit formation. Transcriptomic analysis revealed dysregulation of genes involved in lipid metabolism, including pathways for cholesterol transport, glycerophospholipids, and ceramide biosynthesis. Metabolomic profiling further identified significant changes in glycerophospholipid and sphingolipid metabolism, highlighting a decline in phospholipid species and ceramide accumulation. Serum analysis of AMD patients revealed altered levels of 18 lipids identified in RPE cultures. Four lipids showed significant differences compared to 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, adj. p value < 0.001), PE(15:0/20:3(5Z,8Z,11Z)) (0.66-fold decrease, adj. p value < 0.05), and PC(22:2(13Z,16Z)/13:0) (0.71-fold decrease, adj. p value < 0.05). These findings underscore the systemic nature of lipid dysregulation in AMD and the translational relevance of the RPE model. Conclusions This study highlights the significant role of lipid metabolism dysregulation in AMD pathogenesis. The consistent lipidomic alterations observed in RPE cultures and AMD patient serum reinforce their potential as biomarkers for disease progression and therapeutic targets. These findings provide a robust framework for understanding AMD-associated lipid metabolism changes and their systemic impact. |
| Related Links | https://bmcbiol.biomedcentral.com/counter/pdf/10.1186/s12915-025-02198-8.pdf |
| Ending Page | 21 |
| Page Count | 21 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17417007 |
| DOI | 10.1186/s12915-025-02198-8 |
| Journal | BMC Biology |
| Issue Number | 1 |
| Volume Number | 23 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2025-04-12 |
| Access Restriction | Open |
| Subject Keyword | Life Sciences Multiomics Ageing Age-related macular degeneration Lipid metabolism Retinal pigment epithelium Serum |
| Content Type | Text |
| Resource Type | Article |
| Subject | Ecology, Evolution, Behavior and Systematics Structural Biology Biochemistry, Genetics and Molecular Biology Plant Science Biotechnology Physiology Agricultural and Biological Sciences Cell Biology Developmental Biology |
| Journal Impact Factor | 4.4/2023 |
| 5-Year Journal Impact Factor | 5.4/2023 |
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