Human ocular carotenoid-binding proteins

Abstract

Two dietary carotenoids, lutein and zeaxanthin, are specifically delivered to the human macula at the highest concentration anywhere in the body. Whenever a tissue exhibits highly selective uptake of a compound, it is likely that one or more specific binding proteins are involved in the process. Over the past decade, our laboratory has identified and characterized several carotenoid-binding proteins from human retina including a pi isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein, a member of the steroidogenic acute regulatory domain (StARD) family as a lutein-binding protein, and tubulin as a less specific, but higher capacity site for carotenoid deposition. In this article, we review the purification and characterization of these carotenoid-binding proteins, and we relate these ocular carotenoid-binding proteins to the transport and uptake role of serum lipoproteins and scavenger receptor proteins in a proposed pathway for macular pigment carotenoid delivery to the human retina.

Fig. 1

Ophthalmoscopic view of a human retina (left) showing the boundaries of the human macula as a 5 mm diameter dashed white circle centered on the fovea. The macular carotenoid pigment is concentrated in the central 500 microns of the macula at the fovea. The chemical structures of the major macular pigment carotenoids are shown on the right.

Fig. 2

(a) Vertical section (vitreous side down) through a monkey fovea showing the distribution of the yellow macular carotenoids. Image courtesy of D. Max Snodderly, PhD. (b) GSTP1 labeling of foveal cones in the macula of a 3-year-old monkey. The orientation of the section is the same as in (a). This montage shows strongest labeling by antibody against GSTP1 (red) over the myoid and ellipsoid regions of cones identified by monoclonal antibody 7G6 (green).

Fig. 3

Possible pathway for MP carotenoid uptake, transport, and accumulation in the human retina. Choroicapillaris (CH); Bruch's membrane (BM); retinal pigment epithelium (RPE); inner segments (IS); outer plexiform layer (OPL); inner plexiform layer (IPL).