Macula zeaxanthin

Schalch, W. (2001). Possible contribution of lutein and zeaxanthin, carotenoids of the macula lutea, to reducing the risk of age-related macular degeneration A review. HKJ Ophthalmology 4 31—42. 

Bhosale, P., A. J. Larson, K. Southwick, C. D. Thulin, and P. S. Bernstein. 2004. Identification and characterization of a Jt-isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye. J. Biol. Chem. 279 4944749454. 

The horizontal distribution (Figure 13.4, top) of the macular xanthophylls across the retina has been studied in detail by measuring concentrations in postmortem eyes via HPLC (Bone et al. 1997). The macular xanthophylls are detectable across the entire retina but have their highest concentration in the center of the macula. The local zeaxanthin to lutein ratio depends on the distance from the fovea and decreases from about 2 1 at its center to a low of near 1 2 in the peripheral retina. The variation in the zeaxanthin/lutein ratio across the retina suggests that the chemical and biochemical influences operating on the xanthophylls in the peripheral retina are different from those in the central macula. This is an area about which not much is known and would constitute an interesting field of research. 

As already mentioned, macular zeaxanthin comprises two stereoisomers, the normal dietary (3/(,37()-/caxanthin and (3f ,3 S)-zeaxanthin(=(meyo)-zeaxanthin), of which the latter is not normally a dietary component (Bone et al. 1993) and is not found in any other compartment of the body except in the retina. The concentration of (tneso)-zeaxanthin in the retina decreases from a maximum within the central fovea to a minimum in the peripheral retina, similar to the situation with (3/ ,37 )-zeaxanthin. This distribution inversely reflects the relative concentration of lutein in the retina and gave rise to a hypothesis (Bone et al. 1997) that (meso)-zeaxanthin is formed in the retina from lutein. This was confirmed by an experiment in which xanthophyll-depleted monkeys had been supplemented with chemically pure lutein or (3/ ,37 )-zeaxanthin (Johnson et al. 2005). (Meyo)-Zeaxanthin was exclusively detected in the retina of lutein-fed monkeys but not in retinas of zeaxanthin-fed animals, demonstrating that it is a retina-specific metabolite of lutein only. The mechanism of its formation has not been established but may involve oxidation-reduction reactions that are mediated photochemically, enzymatically, or both. Thus, (meso)-zeaxanthin is a metabolite unique to the primate macula. 

The observation that lutein and zeaxanthin occur in the highest concentration in the macula soon raised expectations that the macular xanthophylls may be essential in maintaining structure and function of the retina by contributing not only to risk reduction of macular diseases but also to improving visual performance of the healthy eye, which was the original hypothesis to explain the presence of the macular yellow pigment as mentioned previously. 

The evidence available to date indicates that lutein and zeaxanthin could contribute to achieving the last two objectives, namely, the reduction of actinic insults caused by blue light and quenching reactive oxygen species. This follows from the dual presence of xanthophylls in the macula their prereceptoral location and their presence within the outer segments themselves, as discussed in Section 13.5. 

However, the metabolic pathways of lutein and zeaxanthin are only beginning to be discovered. Several derivatives of dietary xanthophylls have been identified in the retina, such as 3 -epilutein, meso-zeaxanthin, 3 -oxolutein, and 3-methoxyzeaxanthin, and it has been suggested that they may be formed as a result of nonenzymatic oxidative modifications (Bernstein et al., 2001,2002b Bhosale et al., 2007b Khachik et al., 1997). The macula lutea contains predominantly meso-zeaxanthin (Figure 15.1), which is believed to originate from either oxidative modification or double bond isomerization of dietary lutein (Khachik et al., 1997, 2002). 

Several studies have linked lutein to a lower risk for eye, skin and other health disorders, probably through its antioxidant activity. Lutein is apparently metabolized to zeaxanthin, an isomer, and several other compounds which protect the macula from ultraviolet radiation. The suggestion is that lutein may play a positive role in reducing macular degeneration. Other reports have linked lutein to a reduction of risk of cancer.13 Regardless, lutein is currently being promoted as an important dietary supplement. 

P-carotene is only one of many antioxidants, which can be detected in the skin. Other carotenoids, for example, lutein and zeaxanthine, are preferentially found in the macula lutea, the so-called yellow spot in the eye. Here, carotenoids are subject to a metabolism typical for that tissue, which cannot be found in other tissues (e.g., formation of meso-zeaxanthine). In addition, they can specifically be absorbed into the macula. In the macula, they protect the retinal pigment epithelial cells against oxidative damage from UV light. Indeed, these two carotenoids can be protective against age-dependent macula degeneration. 

Skin carotenoid levels, however, do not correlate with ocular levels of lutein and zeaxanthin which are likely to be concentrated in the macula by specific binding proteins. Therefore it is necessary to develop separate detection technology for the macular pigment measurements. 

Bone et al.20 originally showed that MP was as highly variable in the infant retina as it is in the adult retina. Z is the dominant carotenoid in the center of the adult retina and L predominates in the periphery (thus, in vivo measures of MP account mostly for zeaxanthin concentration). This ratio appears to be reversed in the infant retina, where L dominates in the center (at this point, of course, the macula is quite immature and similar to the periphery). Although all of the factors responsible for the wide variation in infant MP have not been studied, dietary intake of L and Z is still clearly necessary. Whereas MP can be manipulated in the adult via intake of xanthophyll-rich foods, the obvious concern with infants is that food options are limited to breast milk or manufactured infant formulas. Breast milk contains at least 300 defined nutrients, whereas most infant formulas contain approximately 60-70 defined nutrients76 Currently, infant formula does not contain L and Z in other than trace amounts,76 and many formulas are completely devoid of L. In contrast, breast milk contains L and Z in concentrations that are approximately proportional to maternal intake of these carotenoids.77 These observations are important since many infants are exclusively formula fed. Johnson et al.21 showed that breast-fed infants and formula-fed infants had the same levels of plasma L and Z at birth. After 1 month, however, plasma L and Z significantly increased for the breast-fed infants and decreased in the formula-fed infants. This implies that retinal levels in formula-fed infants are also low. 

There is much current debate about the relevance of such carotenoid repair processes to hydrocarbon carotenoids such as 8-carotene and lycopene in vivo where the parent carotenoid is unhkely to encounter the polar ascorbic acid. However, the cation radical, with a positive charge, maybe sufficiently polar and long-lived for such interactions to be possible. For the carotenoids found in the macula, where an efficient anti-oxidant process is crucial, the hydroxy carotenoids zeaxanthin, meso zeaxanthin and lutein are likely to be in a membrane orientation such that the corresponding cation radicals are efficiently repaired by the vitamin C (cf. vitamin E, below). 

Two essential carotenoids, lutein and zeaxanthin, play an important role in the visual process. For the treatment of age-related macular degeneration (AMD), knowledge of the isomeric composition within the macula is of particular interest [7], Full assignment of isomeric configuration is possible by the registration of two-dimensional proton-proton correlated NMR spectra. Figure 7-7 shows, as an example, the COSY stopped-flow NMR spectrum of all-trans zeaxanthin isolated from ox retina. 

Lutein (6) and Zeaxanthin (9) in Kiwifruit Improvement and Protection on Human Macula and Retina... 

---