Plasmalogen deficiency is associated with major polyunsaturated fatty acid (PUFA) alterations in the mouse retina

Background: Plasmalogens are ether-phospholipids that play essential roles in cell physiology. They serve as reservoirs for polyunsaturated fatty acids (PUFAs), which regulate retinal vascular development. Plasmalogen deficiency is associated with severe ocular defects in mice, including abnormal retinal vascularization. However, the impact of plasmalogen deficiency on retinal fatty acid composition remains to be determined. Objectives: This study evaluated the effects of plasmalogen deficiency on mouse retinal fatty acid composition and whether dietary supplementation of lactating mothers with a plasmalogen precursor, alkylglycerol, could prevent these alterations in offspring. Because the retina is an extension of the central nervous system, the brain cortex was also analyzed to compare tissue-specific responses to plasmalogen deficiency. Methods: Lactating mice were fed a diet enriched with 2% alkylglycerols. Retinal and brain fatty acid compositions were determined in pups at postnatal day 21 using gas chromatography with flame ionization detection (GC-FID). Results: Plasmalogen deficiency was associated with significant alterations in retinal fatty acid composition. Total PUFAs content was significantly reduced, while the n−6:n−3 ratio was strongly increased. These changes were accompanied by modest but significant increases in saturated and monounsaturated fatty acids. Alterations of PUFAs composition were also observed in the cortex. Maternal alkylglycerol supplementation showed only a slight trend toward improvement and was insufficient to restore retinal plasmalogen levels, PUFA content, or n−6:n−3 ratio. In the brain, alkylglycerol supplementation had no effect, suggesting potential tissue-specific differences in precursors uptake/metabolism. Conclusions: Plasmalogen deficiency significantly disrupts the fatty acid composition of the retina, primarily through PUFA depletion and an increased n−6:n−3 ratio. These alterations may contribute to the pathological retinal phenotype observed in plasmalogen-deficient mice. Maternal alkylglycerol supplementation during early postnatal life is insufficient to correct these defects. Further studies are needed to clarify the role of altered lipid composition in retinal vascular development.