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Ashley S. Davis, Amit K Patel, Abigail S Hackam; Investigating the Protective Effects of Dietary Supplementation in Retinal Degenerations. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5758.
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Retinal degenerative diseases affect over 5 million people in the US and cause blindness due to photoreceptor death. An effective nutritional therapy would create the possibility of disease prevention without the potential side-effects that occur with pharmaceutical interventions. The purpose of this study was to test whether a diet supplemented with grapes in the form of chemically defined freeze-dried grape powder (FDGP) protected photoreceptors in two mouse models of retinal degeneration.
The rd10 genetic model was analyzed at post-natal days (P)18 to P32. The induced oxidative stress model, using subretinal injection of 1 mM paraquat (PQ) in C57Bl/6 mice, was analyzed at 2 weeks post injury. Mice were fed the grape-supplemented diet, sugar-matched control diet, or normal chow control diet, from birth for the rd10 mice, and for 5 weeks prior to injury for the PQ-injured mice. Photoreceptor function was analyzed using ERGs and retinal outer nuclear layer (ONL) thickness was measured using optical coherence tomography. Protein levels were analyzed by Western blots on whole retinas.
rd10 mice fed the grape-supplemented diet showed up to 3-fold higher rod and cone photoreceptor responses when compared with the control diets (N=4-7, p<0.001). Retinas from rd10 mice in the grape diet group at P21 showed a 100% increase in β-catenin and a 25% reduction in GSK3β (N=5,3), suggesting an increase in neuroprotective Wnt signaling by grape supplementation. The rd10 mice on the grape diet also had a 40% decrease in phospho-P65 NFkB and a 20% decrease in the microglia marker IBA1 (N=5,3), suggesting reduced inflammatory responses. The grape diet also significantly rescued the retina in the PQ-induced model. The grape diet mice injected with PQ had up to 2-fold higher photoreceptor responses (N=8,8, p<0.05) and 17% thicker ONL compared with control mice injected with PQ (N=8,7, p=0.05).
These results demonstrate that a diet supplemented with grapes significantly protected retinal structure and function in two different mouse models. The mechanism of protection by grapes may involve increased neuroprotective Wnt signaling and decreased retinal immune response. This study indicates the possibility of grape supplementation as a nutritional therapy for retinal degeneration.
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