Lipidomic analysis of the retina in a rat model of Smith–Lemli–Opitz syndrome: alterations in docosahexaenoic acid content of phospholipid molecular species

摘要: Smith-Lemli-Opitz syndrome (SLOS) is a complex hereditary disease caused by an enzymatic defect in the last step of cholesterol biosynthesis. Progressive retinal degeneration occurs AY9944-induced rat model SLOS, with biochemical and electroretinographic hallmarks comparable to human disease. We evaluated alterations non-sterol lipid components retina this model, compared age-matched controls, using lipidomic analysis. The levels 16:0–22:6 18:0–22:6 phosphatidylcholine molecular species retinas were less >50% >33%, respectively, rats treated for either two or three months AY9944. Relative AY9944 treatment resulted >60% di-22:6 >15% phosphatidylethanolamine species. predominant phosphatidylserine control di-22:6; notably, >80% phosphatidylserine, relative controls. Remarkably, these changes occurred absence n3 fatty acid deficiency plasma liver. Thus, lipidome globally altered SLOS rats, most profound being phosphatidylcholine, phosphatidylethanolamine, containing docosahexaenoic (22:6). These findings suggest that may involve additional metabolic compromise beyond primary pathway.