Carotenoid Uptake and Protection in Cultured RPE - Carotenoids: Physical, Chemical, and Biological Functions and Properties - page 311

retina—photoreceptor outer segments (POS) and retinal pigment epithelium (RPE) (Rapp et al.,
2000; Sommerburg et al., 1999).
Some observational epidemiological studies have shown a reduced risk of age-related macu-
lar degeneration (AMD) or rate of its progression in people with a higher intake and/or higher
plasma concentrations of lutein and zeaxanthin (Delcourt et al., 2006; Goldberg et al., 1988; Moeller
et al., 2006; Nolan et al., 2007; SanGiovanni et al., 2007; Seddon et al., 1994; Snellen et al., 2002;
Sperduto, 1993; Tan et al., 2008; van Leeuwen et al., 2003). AMD is the leading cause of blindness
in people above 60 years old in the developed countries and becomes an increasingly important
socio-economic problem due to ageing populations of extended lifespans.
AMD is a progressive disease that affects RPE and photoreceptors in the central part of the
retina. Initial changes include formation of deposits between RPE and Bruch's membrane, so-called
drusen, and/or pigmentary abnormalities in the RPE. Even though at that stage the vision is not
affected, the changes are a strong predictor of developing of the advanced form of AMD and there-
fore, the stage when they are present is usually referred to as early AMD. The disease progresses
when drusen become more numerous, and eventually conl uent, and RPE cells die leaving depig-
mented areas in a process called geographic atrophy, which are often surrounded by areas with an
increased pigmentation. This form of the disease, called the “dry” form, is present in about 90%
of AMD victims. In 10% of AMD patients, new blood vessels from the choroid invade the retina
leading to the rapid progression of vision loss in the so-called “wet” form of the disease.
Despite recent i ndings of several genes associated with AMD (Edwards, 2008; Lotery and
Trump, 2007; Moshfeghi and Blumenkranz, 2007; Mullins, 2007; Scholl et al., 2007; Swaroop
et al., 2007), the etiology of the disease still remains largely unknown and involves a complex
interaction of genetic and environmental factors (Gorin, 2007). Current anti-angiogenic treatments
target only the so-called “wet” form of the disease (Owens et al., 2006). There is no effective pre-
vention or treatment for the atrophic form of the disease affecting the majority of AMD victims
(reviewed by Chong et al. (2007), Coleman and Chew (2007), Donaldson and Pulido (2006), Eter
et al. (2006), Guymer and Chong (2006), and Yeoh et al. (2006)). The only widely used approach
is supplementing AMD patients with a combination of zinc, vitamin C, vitamin E and b-carotene.
This mixture has been tested in a large clinical trial, the Age-Related Eye Disease Study (AREDS),
where the effects of supplementation on the progression of AMD and vision loss were followed for
up to seven years (AREDS, 2001). The participants were randomly allocated placebo, zinc and/or
antioxidant mixture of b-carotene with vitamin C and E. Supplementation with zinc alone reduced
the risk of progression to advanced AMD by 20%, while antioxidant mixture composed of about
15 mg of b-carotene, 400 IU vitamin E and 500 mg vitamin C reduced the risk by 17%. Combined
zinc and vitamin C, vitamin E and b-carotene reduced the risk by 25%, and only these results were
statistically signii cant. While in the published report from the study it is mentioned that during the
trial some participants assigned to antioxidant supplements opted for mixtures without b-carotene,
no further data on that group of patients were provided. Therefore, the data available are not conclu-
sive whether b-carotene is an essential component of the AREDS mixture to be protective against
progression of AMD. Further evaluation of whether b-carotene is needed as a component of the
AREDS mixture will be tested in a multicenter controlled, randomized trial—the Age-Related Eye
Disease Study 2 (AREDS2). Other trials, testing the effects of supplementation with b-carotene
alone or in a mixture with other antioxidants, did not show any statistically signii cant differences
on AMD development between supplemented and non-supplemented groups of people (Evans,
2006; West et al., 2006).
As the therapy of AMD is very limited, there is an urgent need to develop an intervention
to prevent vision loss. The epidemiological data together with the well-documented antioxidant
properties of carotenoids in studies in vitro and with proven increases in macular pigment density
in most people via dietary supplementation (Beatty et al., 2004; Berendschot et al., 2000; Bone
et al., 2003; Hammond et al., 1997; Iannaccone et al., 2007; Landrum et al., 1997), including
patients with early AMD (Koh et al., 2004; Obana et al., 2008; Richer et al., 2007; Trieschmann