Blood lipidomics in age-related macular degeneration: insights into phospholipids, cholesteryl esters and n-3 polyunsaturated fatty acid supplementation

Abstract

Purpose : Age-related macular degeneration (AMD) is a complex disease that has been associated with several changes in lipid metabolisms. Moreover, evidence from population studies shows that an increased dietary supply in n-3 polyunsaturated fatty acids (PUFAs) is protective against both, initiation and progression of AMD. The objective of this study was to use an untargeted lipidomic approach to identify the blood lipidomic signature associated with AMD and to check whether it is affected by n-3 PUFA supplementation.

Methods : One hundred and twenty-two participants were recruited in the context of the FATTY case-control study (NCT04278300). Lipids were extracted from total blood and lipidomic profiles were determined using ultra-performance liquid chromatography in reversed phase (C18) coupled with high-resolution mass spectrometry (UPLC-HRMS). Analyses were conducted separately in both positive and negative ionization modes, using MS and MS/MS acquisition.

Results : Significant changes in 15 lipid metabolites, including 11 phospholipids (GPs), were observed between non-supplemented AMD subjects and controls. In subjects with AMD that were supplemented with n-3 PUFAs, significant modifications in 65 lipid metabolites, with 21 exhibiting decreased levels and 44 showing increased levels were observed. Notably, 30 of the increased lipid species contained n-3 PUFAs such as docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) on GPs and cholesteryl esters (CEs), thus reflecting the oral supplementation. Further targeted analysis of CEs confirmed these findings.

Conclusions : Through an untargeted approach, this study identified a global lipidomic blood signature for AMD and the impact of n-3 PUFA supplementation on it. This work confirms that GPs and CEs are key actors for the blood transport of orally-delivered n-3 PUFAs.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.