Long-term treatment with 9-cis-β-carotene rich alga Dunaliella bardawil ameliorates photoreceptor degeneration in a mouse model of retinoid cycle defect

Abstract

The retinoid cycle is the enzymatic pathway that regenerates the vision chromophore, 11-cis retinal, after it is bleached during light absorption. Genetic insults to this cycle result in incurable blinding retinal dystrophies such as retinitis pigmentosa and Leber congenital amaurosis. Previous studies demonstrated that oral treatment with 9-cis-β-carotene rich Dunaliella bardawil powder significantly improved visual and retinal function in patients with fundus albipunctatus night blindness and retinitis pigmentosa. Here we examined the effect of oral treatment with the Dunaliella powder on retinal function and structure in RPE65rd12 mice, a model of a genetic defect in the retinoid cycle. Mice were fed with a control diet, vitamin A deficient diet (VAD) or VAD diet supplemented with Dunaliella powder for 13 months. Mice fed with Dunaliella presented significantly higher dark-adapted (35.7 μV ± 3.1 vs. 6.9 μV ± 2.5, p < 0.001 for VAD and vs. 4.3 μV ± 1.1, p < 0.001 for control) and light-adapted (35.1 μV ± 4.3 vs. 6.2 μV ± 3.0, p < 0.001 for VAD and vs. 4.9 μV ± 1.3, p < 0.001 for control) maximal electroretinogram a-wave amplitudes. The Dunaliella group also presented higher dark- and light-adapted maximal electroretinogram b-wave amplitudes compared with the control diet (86.5 μV ± 9.4 vs. 28.7 μV ± 6.3, p < 0.001 and 79.2 μV ± 10.4 vs. 28.3 μV ± 4.7, p = 0.001, respectively), but comparable results to the VAD group. A significantly higher number of M-cone photoreceptors was identified in the retinas of DUNA treated mice. Taken together, our study suggests that 9CBC-rich Dunaliella bardawil powder may present an effective treatment for retinal dystrophies caused by defects in the retinoid cycle.