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.

Macular Pigment Imaging in AREDS2 Participants: An Ancillary Study of AREDS2 Subjects Enrolled at the Moran Eye Center

“…This result emphasizes that the deposition of lutein and zeaxanthin in the human macula is a specific high-affinity process mediated by binding proteins such as GSTP1 and StARD3, whereas skin deposition of carotenoids is a much less specific process that tends to reflect serum carotenoid concentrations with a preference for the nonpolar carotenes and lycopene relative to the more polar xanthophylls lutein and zeaxanthin. [8][9][10]31,36 The major limitation of this study is the relatively small number of subjects, which decreases the power to perform statistical analyses beyond simple linear regressions. Moreover, our Utah cohort may not be representative of the entire AREDS2 population.…”

“…7 This is because uptake and stabilization of lutein and zeaxanthin in the macula are complex, biologically regulated processes mediated by specific binding and transport proteins. 8 This means that macular uptake of lutein and zeaxanthin is subject to saturation effects and is dependent on protein expression levels and binding affinities of the proteins' various isoforms. Our laboratory has identified GSTP1 as the specific binding protein for zeaxanthin in the primate macula, and we have recently identified StARD3 as the specific luteinbinding protein.…”

Measurments of Carotenoid Levels in Human Serum and a Catalog of the Lutein Conformation Populations from Semi-empirical Calculations

“…selection of these carotenoids is probably determined by the selective binding proteins GSTP1 [24] (glutathione s-transferase P1) and StARD3 (steroidogenic acute regulatory domain protein 3) to mediate this process [26]. Experiments show that human GSTP1 exhibits a high affinity for zeaxanthin, and human StARD3 proteins bind lutein.…”

“…A clear pathway of how these carotenoids are transported to the retina is still not well-defined. Li et al [24] proposed a possible pathway for the uptake, transport and accumulation of these macular pigments carotenoids in the retina based on their studies on carotenoid-binding proteins. They suggest that the uptake of carotenoids within the cholesterol containing lipoproteins is mediated by HDL and HDL receptors, such as SR-BI (a cell surface glycoprotein that binds HDL).…”

“…Carotenoids can also be captured by extra-hepatic tissues before they are taken to the liver. Lutein and zeaxanthin will be transported with HDL in the bloodstream, and the uptake of lutein and zeaxanthin on RPE cells will be mediated by the SR-B1 (scavenger receptor class B member 1, is a receptor for HDL) [24]. The …”