RPE65 takes on another role in the vertebrate retina

Abstract

The high-acuity central vision of humans, and other primates, depends on a region of the central retina called the macula lutea (Latin: yellow spot), containing not only a high concentration of both cone and rod photoreceptors but also a high concentration of xanthophyll carotenoids; hence, its name (1). At the center of the macula is the fovea (Latin: pit) centralis, a region of especially high-acuity vision, containing only cone photoreceptors and Muller glia cells, where, in the human fovea, the density of cones is estimated to reach 1–3 × 105 per square millimeter. In the fovea, there are no overlying interneurons or retinal ganglion cells, as in the rest of the retina. Instead, the axons of the foveal cones are elongated and connect to bipolar cells located on the rim of the foveal pit. Anatomically, these elongated axonal processes form a layer called the fibers of Henle that overlies the cone photoreceptors like a thin cap. It is here that the macular xanthophylls accumulate (2). It is thought that the protective function of the xanthophylls is twofold: serving as a blue-light filter and as scavengers of reactive oxygen species (ROS), both potentially damaging to cone photoreceptors (3). The electron-rich polyene chains of carotenoids efficiently quench ROS, thereby preventing membrane damage. Three xanthophylls are found in the macula and fovea: two, lutein and zeaxanthin, are abundant in nature, while the third, meso -zeaxanthin, is uncommon elsewhere outside primate and bird retinas (although synthetic meso -zeaxanthin is now commercially available). Both zeaxanthins have a better singlet oxygen-quenching ability than lutein due to an additional conjugated double bond, while meso -zeaxanthin may have the greatest antioxidant ability of the three (4). Threats to the health of the macula, and vision itself, include various inherited simple Mendelian gene disorders, all relatively … [↵][1]1Email: redmondd{at}helix.nih.gov. [1]: #xref-corresp-1-1