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property. It was estimated that the MP can attenuate up to 40% of the blue light that hits the macula
(Krinsky et al. 2003). The antioxidant properties of the macular xanthophylls have been demon-
strated many times. They can quench singlet oxygen as well as other reactive oxygen intermedi-
ates (Krinsky and Deneke 1982) and an oxidized metabolite of lutein, 3
′
-dehydro-lutein, has been
identii ed in plasma and in the retina (Khachik et al. 1997a).
Xanthophylls can further inhibit the peroxidation of membrane phospholipids (Lim et al. 1992) and
reduce photooxidation of lipofuscin l uorophores (Kim et al. 2006), which are implicated in the patho-
genesis of AMD (Sparrow and Boulton 2005). Furthermore, it was shown that light-induced damage
to photoreceptors was reduced in quails fed zeaxanthin, with the number of apoptotic photoreceptor
cells being inversely related to the concentration of zeaxanthin in the retina (Thomson et al. 2002).
Results of human epidemiological studies investigating the relationship of MPOD and dietary
or supplemental intake of lutein and zeaxanthin with the risk of AMD are somewhat variable,
presenting a mixed picture and not all studies were able to generate supportive evidence (van den
Langenberg et al. 1998, Flood et al. 2002, Cho et al. 2004). This is not surprising in view of the fact
that AMD is a degenerative disease that develops over a lifetime with many confounding factors
prevailing making an epidemiological assessment difi cult. Early data indicated that subjects with
low dietary intake (Seddon et al. 1994) or plasma levels (EDCC Study Group 1993) of macular xan-
thophylls had a higher risk for neovascular AMD. These results are consistent with a more recent
evaluation by Snellen et al. (2002) of the prevalence of AMD in relation to antioxidant and xan-
thophyll intake. They reported a dose-response relationship with higher xanthophyll intakes exhib-
iting lower prevalence rates. A more recent epidemiological study investigating the relationship of
plasma levels of xanthophylls and the risk for AMD (Delcourt et al. 2006) indicated that subjects in
the south of France had a lower risk for AMD if they had higher plasma concentrations particularly
of zeaxanthin, coni rming results of Gale et al. (2003) in a U.K. population. An epidemiological
evaluation of data from the Age-Related Eye Disease Study (AREDS) indicated that subjects in the
highest quintile of dietary lutein and zeaxanthin intake had a statistically signii cant lower risk of
developing different manifestations of AMD (AREDS Research Group et al. 2007).
Some studies have reported lower MPOD in AMD eyes or in eyes at risk of developing AMD
(Schweitzer et al. 2000, Beatty et al. 2001, Bernstein et al. 2002, Obana et al. 2008) by using differ-
ent noninvasive measuring techniques in the living eye. In contrast, Bone et al. (2001) have deter-
mined lutein and zeaxanthin directly in postmortem retinal tissue samples by HPLC from normal
subjects and subjects with AMD. The results demonstrated that the average lutein and zeaxanthin
levels were lower in the AMD retinas than in the normal retinas. Those individuals with the highest
quartile of xanthophyll concentration in the outer annulus had an 82% lower risk for AMD when
compared to those in the lowest quartile (Landrum et al. 1999b). Because this relationship was
found in the outer annulus which is relatively unaffected by AMD, this observation lends support
to the conclusion that the observed reduction of MPOD may be preceding the disease rather than
resulting from the disease. Thus, low carotenoid concentrations in the retina can be a risk factor for
AMD. How and to what extent the quantitative amount of carotenoids in the macula modulates an
individual's AMD risk is still open to debate.
The question of how exposure to sunlight contributes to the etiology of AMD was recently
investigated together with plasma concentration of antioxidants including lutein and zeaxanthin.
This was done in course of the EUREYE study conducted in 4750 subjects older than 65 years
from across Europe. The participants were interviewed for their lifetime sunlight exposure and
gave a plasma sample for biochemical analyses. The results of the study indicated a strong inverse
association of sunlight exposure and neovascular AMD, particularly in subjects with low antioxi-
dant plasma levels with odds ratios being as high as 3.72 for subjects low in vitamins E and C and
zeaxanthin (Fletcher et al. 2008). Furthermore, odds ratios for AMD in this study were generally
increased for almost every combination of lower lutein and zeaxanthin plasma concentrations.
Overall, a substantial number of epidemiological and experimental studies suggests that lutein
and zeaxanthin could contribute to risk reduction of AMD. Two recent articles in this respect appear
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