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Mandy Hong, Sharee Kuny, Rachel Bryant, Frederic Gaillard, Miyoung Suh, Yves Sauve; The Effects of Docosahexaenoic Acid (DHA) Dietary Supplementation on Retinal Lipid Profile in a Mouse Model of Stargardt-like Macular Dystrophy (STGD3). Invest. Ophthalmol. Vis. Sci. 2013;54(15):4084.
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© ARVO (1962-2015); The Authors (2016-present)
Accumulating evidence demonstrate that docosahexaenoic acid (DHA) can delay the progression of age-related macular degeneration (AMD); however, the underlying mechanisms remain unknown. Using the ELOVL4 mouse, an animal model of early onset macular degeneration (Stargardt-like, STGD3), we examined the impact of DHA supplementation on retinal anatomy, function, and lipid profile. We hypothesized that antenatal DHA supplementation in ELOVL4 mice would optimize DHA’s rescue effect on the retina as evidenced by preserved function, anatomy and lower AA/DHA ratios.
Wildtype (WT) and transgenic (TG) mice were provided DHA+ (1% over total fatty acid content), DHA- (DHA replaced with oleic acid), or chow (0.19% omega-3 fatty acid, standard laboratory diet) antenatally. Electroretinograms (ERG), cross-sectional staining, and ultrahigh-pressure liquid chromatography coupled with mass spectrometry coupled with mass-spectrometry (UPLC-MS-MS) allowed assessment of retinal function, anatomical integrity, and fatty acid profiles, respectively. ERGs were recorded at 1 and 3 months of age, while the other outcome measures were obtained at 3 months.
ERG and anatomical results showed rod dysfunction (at 1 and 3 months) and photoreceptor loss (at 3 months only) in TG versus WT mice. Diet did not affect retina function in WT or TG mice. Paradoxically, the number of photoreceptors was reduced and the AA/DHA ratio increased in DHA versus non-DHA supplemented TG mice. This effect was not observed in WT animals.
Expression of the human mutated ELOVL4 in mice exerts a negative impact on retinal function and anatomy, occurring as early as 1 and 3 months, respectively. While exogenous DHA intake is essential for eye development, dietary levels of 1% or more might be associated with negative effects on photoreceptor survival and function during development in subjects with STGD3.
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