Chemistry Reference
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this condition, but recently a probable gene may have been identii ed (Yang et al. 2008). Neovascular
or exudative AMD, the “wet” form of AMD, causes vision loss due to abnormal blood vessel growth
(angiogenesis) beneath and into the macula. These newly formed blood vessels are imperfect and
blood leaks from them causing blood accumulation under the retina, which leads to irreversible
damage to the functional layers of the macula. Finally, vision is completely lost if the condition is
left untreated. An effective but very expensive treatment regimen for this neovascular (“wet”) form
of AMD has recently become available. However, an intervention that would prevent or at least slow
the progression of this disease would certainly be a welcome alternative (de Jong 2006).
The etiology of AMD is not completely understood, but some ideas regarding its pathogenesis
have been developed. Photoreceptors are constantly exposed to (photo)-oxidative damage in the
environment of the retina, which is characterized by the simultaneous presence of light and oxygen.
As a consequence, they are damaged and become dysfunctional. Before new photoreceptors can be
formed, dysfunctional photoreceptors must be disposed of. This task is accomplished by the highly
metabolically active RPE cells. It is estimated that during a period of about 10 days, each RPE
cell has to phagocytose, digest, and eliminate into the blood l ow about 50 photoreceptors. Thus,
during 60 years, more than 100,000 photoreceptors are to be processed by a single RPE cell. It is
not surprising that during this very dynamic metabolic activity, digestion, and elimination of spent
photoreceptors is not always complete and cell debris accumulates, mostly in the form of lipofuscin
and its derivates, causing a progressive malfunctioning and eventual death of not only the RPE but
also of the photoreceptor cells (Sun and Nathans 2001).
Logical targets for risk reduction and prevention of AMD appear to include support to the RPE
cells so that they are better able to cope with their exceptional metabolic burden, the reduction of
the generation of new but imperfect blood vessels by inhibiting angiogenesis, reduction of blue light
which has the highest damage potential of the visible light reaching the macula, and reduction of
oxidative damage by antioxidants.
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.
Recent experimental evidence indicates that lutein and zeaxanthin may be instrumental in main-
taining a healthy RPE. Rhesus monkeys raised on a xanthophyll-free diet since birth exhibited a
distorted proi le of the RPE cells in the macula, with a reduced cell density in the center of the
fovea, whereas normally the maximum density of RPE cells is to be found there (Leung et al. 2004).
Supplementation of the animals with lutein or zeaxanthin altered the RPE cell proi le in a way that is
consistent with a migration of RPE cells toward the fovea, and appears to have induced a “normaliza-
tion” of the RPE cell proi le. In a recent publication (Izumi-Nagai et al. 2007), a state of choroidal neo-
vascularization was induced in mice by laser photocoagulation and it was shown that mice pretreated
with lutein were protected from this neovascularization and that a number of inl ammatory biomark-
ers were suppressed. Furthermore, in diabetic mice treated with zeaxanthin, the diabetes-induced
retinal oxidative damage could be reduced along with a decrease of VEGF (Kowluru et al. 2008).
The main parameter used to assess the amount of xanthophylls in the retina is the MPOD.
Recently, a comprehensive review (Nolan et al. 2007b), which demonstrated that age, smoking, and
a family history of AMD were all correlated with a reduced MPOD in a statistically signii cant
manner, was published. Although these correlations do not necessarily signal a causal relationship
they provide suggestive evidence for the contribution of xanthophylls to risk reduction of AMD.
However, the possible contribution of lutein and zeaxanthin to risk reduction of AMD is supported
by experimental, epidemiological, and clinical evidence as described in the following sections.
13.8.2.1 Experimental and Epidemiological Evidence
The contribution of lutein and zeaxanthin to the risk reduction of AMD is mainly based on two
properties of the xanthophylls: one is their blue-light absorption and the other is their antioxidant
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