Abstract
Purpose :
The macular carotenoids, lutein, zeaxanthin and meso-zeaxanthin, are highly concentrated in the human fovea, a retinal region rich in cone photoreceptors. To determine if macular carotenoids are accumulated preferentially in the cone cells, we investigated the carotenoid status in the retinas of mice dominant in either rod or cone cells.
Methods :
Bco2-/- mice can accumulate carotenoids in their retina, where rod cells are the dominant photoreceptors. To establish a mouse model with a dominance of cone cells and the capacity to accumulate retinal carotenoids, Bco2-/- mice were crossed with Nrl-/- mice to create the Bco2/Nrl double knockout mice (Bco2-/-/Nrl-/-). Photoreceptor cells in both mouse strains were identified using immunohistochemistry (IHC), with rod cells labeled using anti-ID4 and cones labeled with anti-S-cone opsin. Subsequently, a carotenoid-feeding experiment was conducted. To enhance carotenoid uptake, six-month-old Bco2-/- and Bco2-/-/Nrl-/- mice (15 mice per group) were maintained on a vitamin A deficient diet for one month, followed by a month of feeding with zeaxanthin. Finally, the retina, RPE/choroid, serum, liver, and brain of these mice were harvested, and carotenoids were extracted from these tissues and analyzed using HPLC.
Results :
Immunohistochemistry (IHC) analysis revealed that rod cells are the predominant photoreceptor cells in Bco2-/- mice, whereas the majority of photoreceptors in Bco2-/-/Nrl-/- mice are cone cells. One month after carotenoid feeding, the zeaxanthin content in the retinas of Bco2-/-/Nrl-/- mice was 2.5 times higher than that in Bco2-/- mice. No significant differences in zeaxanthin levels were observed in the serum, liver, and RPE/choroids between these two groups of mice. Interestingly, the ablation of NRL resulted in a 3.8-fold increase in zeaxanthin in the brains of Bco2-/- mice.
Conclusions :
Our data suggest that macular carotenoids preferentially accumulate in cone photoreceptors. These findings may contribute to a better understanding of the physiological role of carotenoids in the human retina.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.