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Y. Sauve, S. C. Mema, S. Kuny, F. Gaillard, K. Zhang, I. M. MacDonald, T. Clandinin; Dietary Docosahexaenoic Acid (DHA) Supplementation in a Mouse Model of Stargardt-like Dystrophy and Wild Type Mice Delays Age-related Changes in Retina Function. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2975.
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To assess the effect of dietary DHA on retina function in a mouse model of Stargardt-like dystrophy undergoing age-related geographic atrophy and lipofuscin accumulation (ELOVL4 mouse, line 2 from Karan et al., PNAS, 2005, 102:4164-4169).
We undertook two separate studies: manipulating dietary DHA from 1 to 3 months of age and from 12 to 18 months of age. Four groups were considered in each study: ELOVL4 mice and wild type (WT) littermates were each divided into two groups, one fed a 0.44% DHA diet (ELOVL4+, WT+), the other fed the same diet without DHA (ELOVL4-, WT-); total fatty acid levels were identical in both diets. At the beginning and end of each dietary manipulation, the electroretinogram (ERG) was recorded under xylazine-ketamine anesthesia, following one-hour dark-adaptation. Comparisons between groups were made using U-test and Kruskall-Wallis test; significance was set at p<0.05.
Plasma and retina DHA levels (percentage of total fatty acids) were increased in WT+ (4.5 ± 0.9, 25 ± 0.13) and ELOVL4+ (5.5 ± 1.7, 27 ± 0.22) compared to WT- (2.6 ± 0.7, 23 ± 0.2) and ELOVL4- (2.8 ± 0.8, 24 ± 0.17); data only available for the 1-3 month study. For this study, ELOVL4+ (n=5) retained higher dark-adapted mixed a-wave amplitudes than ELOVL4- (n=6). In addition, dark-adapted responses to a probe flash preceded by a bleaching flash (double flash protocol) retained higher b-wave amplitudes in ELOVL4+ compared to ELOVL4-; no differences were seen between WT+ (n=7) and WT- (n=7). For the 12-18 months study, both ELOVL4+ (n=6) and WT+ (n=5) retained higher ERG amplitude when compared to ELOVL4- (n=4) and WT- (n=5), respectively. Amplitude preservation was observed for dark-adapted b-waves isolated with a double flash protocol as well as for photopic b-waves.
Both littermate WT and ELOVL4 mice, fed a DHA supplemented diet, demonstrate a delay in age-related changes in retina function when compared to non-DHA supplemented littermate WT and ELOVL4 mice, respectively. Our findings imply that DHA supplementation could have a broad therapeutic application, which would bypass the primary defect found in the ELOVL4 mouse model of STGD3. Studies on how these preserved ERG response amplitudes translate into visual perception are required to further test the potential benefit of DHA dietary supplementation on age-related changes in visual function.
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