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Maria Esperanza Esperanza Rodriguez Escalante, Tinthu Lee, Ashley Davis, Amit K Patel, Abigail Hackam; A diet supplemented with grapes preserves photoreceptor function in mouse models of retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4361.
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Several studies have suggested neuroprotective benefits from specific diet supplementation in patients with age-related macular degeneration. The effect of diet on photoreceptor survival in mouse models of retinal degeneration has not been described. In this study, we tested whether a diet supplemented with grapes regulates photoreceptor function and survival in two mouse models of retinal degeneration.
The rd10 genetic model of retinitis pigmentosa was analyzed at post-natal days (P)18, P24 and P32. In the acute oxidative stress model, photoreceptor injury was induced by subretinal injection of 1 mM paraquat (PQ) in C57Bl/6 mice, and the mice were analyzed at 2 weeks post injury. Mice were fed the grape-supplemented diet in the form of chemically defined freeze-dried grape powder (FDGP), sugar composition-matched control diet, or normal chow control diet, from birth for the rd10 mice, and for 5 weeks prior to injury for the PQ-injected mice. Photoreceptor function was analyzed using ERGs and retinal outer nuclear layer (ONL) thickness was measured using optical coherence tomography. Levels of cell survival regulators were analyzed by Western blots on whole retinas.
rd10 mice fed the grape-supplemented diet showed significantly higher rod and cone maximum b-wave amplitudes, indicating elevated photoreceptor responses, when compared with the control diets at each timepoint (N=8, p<0.05). Additionally, implicit times for b-waves were lower in the grape diet (p<0.05), which indicates increased photoreceptor function. The oxidative stress-induced PQ-injected mice on the grape diet also showed significantly higher ERG responses (N=8, p<0.05) and thicker outer nuclear layers (N=8, p<0.05). The retinas from rd10 mice on the grape diet showed significant lower phospho-GSK3β levels (p<0.05), whereas the oxidative stress-induced mice had significantly higher phospho-GSK3β levels, compared with mice that were on the control diet.
The grape-supplemented diet improved photoreceptor function in two models of retinal degeneration and the mechanism of protection by grapes may involve differential regulation of GSK3β-dependent signaling pathways. Therefore, our study suggests the possibility of grape supplementation as an adjuvant nutritional therapy for the prevention of retinal degenerative diseases.
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