Retinyl ester homeostasis in the adipose differentiation-related protein-deficient retina

Abstract

The retinal pigmented epithelium (RPE) plays an essential role in vision, including storing and converting retinyl esters of the visual chromophore, 11-cis-retinal. Retinyl ester storage structures (RESTs), specialized lipid droplets within the RPE, take up retinyl esters synthesized in the endoplasmic reticulum. Here we report studies of mice lacking exons 2 and 3 of the gene encoding adipose differentiation-related protein (Adfp), a structural component of RESTs. We found that dark adaptation was slower in Adfp Δ2-3/Δ2-3 than in Adfp+/+ mice and that AdfpΔ2-3/Δ2-3 mice had consistently delayed clearances of all-trans-retinal and all-trans-retinol from rod photoreceptor cells. Two-photon microscopy revealed aberrant trafficking of all-trans-retinyl esters in the RPE of AdfpΔ2-3/Δ2-3 mice, a problem caused by abnormal maintenance of RESTs in the dark-adapted state. Retinyl ester accumulation was also reduced in AdfpΔ2-3/Δ2-3 as compared with Adfp+/+ mice. These observations suggest that Adfp plays a unique role in vision by maintaining proper storage and trafficking of retinoids within the eye. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc.