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N. Acar, P. Sicard, C. Joffre, A.M. Bron, B. Lauzier, C. Vergely, L. Rochette, C.P. Creuzot–Garcher, L. Bretillon; Increased Oxidative Stress Is Responsible for Ether–Lipid Loss in the Retina of Senescence Accelerated Mouse (SAM) . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2088.
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© ARVO (1962-2015); The Authors (2016-present)
Ether–lipids represent an important class of retinal phospholipids but their exact functions are still unknown. They might act as antioxidants since the vinyl–ether double bond they contain could be the target for newly formed oxygenated radicals. In this work, we investigated the status of ether–lipids and aldehydes, their oxidative degradation products in the retina of a mouse model for aging, the senescence–accelerated mouse prone 8 (SAM P8), in which we reported a reduction of retinal function following 12 months of age (ARVO 2004 E–abstract 797). We completed this study by evaluating the oxidative stress in the retina.
The quantification of ether–lipids and aldehydes was achieved by gas chromatography–mass spectrometry (GC–MS) in SAM P8 in comparison to SAM resistant 1 control animals (SAM R1). Superoxide anion and nitric oxide were localized in retinal sections by dihydroethidium (DHE) and 4–amino–5–methylamino–2’,7’–dichlorofluorescein (DAF–FM) staining, respectively. By means of comparison, the production of nitric oxide and superoxide anion in circulating leukocytes was determined by flow cytometry using oxidative fluorescent probes (DAF–FM and DHE).
SAM P8 exhibited a decrease in retinal ether–lipid content and a counterbalanced accumulation of their oxidative degradation products at 5 and 12 months. Increased oxidative stress (up to +40% for superoxide anion) was observed in retinal ganglion cells of SAM P8 in comparison to SAM R1. On the other hand, SAM P8 leukocytes exhibited a significant increase in nitric oxide but not in superoxide anion production, suggesting specific oxidizing and anti–oxidizing mechanisms in the retina.
Based on their putative functional role in the retina, the oxidation of ether–lipids may help to better understand the visual defects observed in SAM P8. Moreover, these results suggest that SAM P8 may be a useful model for evaluating the relationships between aging and oxidation in the retina.
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