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M. Suh, Y. Sauve, C. Murray, J. X. Kang, D. W. L. Ma; The Effect of Enriched Retinal Docosahexaenoic Acid and n-3 Very Long Chain Fatty Acids (VLCFA, C24-C26) on the Electroretinogram in Fat-1 Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2848.
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Fat-1 mice can convert n-6 to n-3 fatty acids endogenously, resulting in an elevated accumulation of n-3 fatty acids in major tissues. We quantified this increase in n-3 fatty acids in the retina and examined how it might impact on retina function.
Both wildtype (WT) and fat-1 mice were fed a modified AIN-93G diet containing 10% safflower oil for 9 weeks. Fatty acid composition of individual phospholipids was analyzed in total lipid extracts from whole eyes (except lens) with GC. Retina function was assessed with electroretinogram (ERG) recordings.
Compared to WT mice, n-3 docosahexaenoic acid (DHA, C22:6n-3) in fat-1 mice was increased 2-5 times (p<0.05) in all phospholipid classes while n-6 fatty acids was decreased by half. Novel component of retinal C32 and C34 of n-3 pentaenoic and hexaenoic VLCFA in phosphatidylcholine was significantly increased whereas n-6 tetra and pentaenoic VLCFA was depleted.Mixed scotopic a-waves (reflecting mainly rod activity) and b-waves (inner retina activity) had higher amplitudes (145% and 136%, respectively); photopic b-waves (cone mediated activity) also had elevated amplitudes (160%) in fat-1 compared with WT mice. In addition, the minimal light levels required to elicit a response (sensitivity) was higher for both rod and cone mediated responses in fat-1 compared with WT mice. Finally, glial fibrillary acidic protein (GFAP) expression (an indicator of retina stress) was increased in fat-1 mice.
These findings indicate that elevated levels of DHA and n-3 VLCFA are associated with elevated amplitude of rod and cone mediated ERG. Association between GFAP expression and n-3 fatty acid content in retina needs further studies. The fat-1 mouse may be a useful model for studying therapeutic strategies to prevent and treat degenerative retinal diseases.
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