LE Magazine May 2002
Page 3 of 4
Influence of lutein supplementation on
macular pigment, assessed with two objective techniques.
PURPOSE: Macular pigment (MP) may protect against
age-related macular degeneration. This study was conducted to
determine the extent of changes in the macular pigment density
as a consequence of oral supplementation with lutein. A second
purpose was to compare two objective measurement techniques.
METHODS: In the first technique, reflectance maps were made
with a scanning laser ophthalmoscope. Digital subtraction of
log reflectance maps and comparison between the foveal area
and a 14 degrees temporal site provided MP density estimates.
In the second technique, spectral fundus reflectance of the
fovea was measured with a fundus reflectometer and analyzed
with a detailed optical model, to arrive at MP density values.
Eight subjects participated in this study. They took 10 mg
lutein per day for 12 weeks. Plasma lutein concentration was
measured at 4-week intervals. RESULTS: After 4 weeks, mean
blood level of lutein had increased from 0.18 to 0.90 microM.
It stayed at this level throughout the intake period and
declined to 0.28 microM 4 weeks after termination. Measurement
of the density of MP showed a within-subject variation of 10%
with MP maps and 17% with spectral reflectance analysis. MP
density showed a mean linear 4-week increase of 5.3% (P: <
0.001) and 4.1% (P: = 0. 022), respectively. CONCLUSIONS:
Supplementation with lutein significantly increased the
density of the MP. Analyzing reflectance maps with a scanning
laser ophthalmoscope provided very reliable estimates of
MP.
Invest Ophthalmol Vis Sci 2000
Oct;41(11):3322-6
Lutein and zeaxanthin concentrations
in rod outer segment membranes from perifoveal and peripheral
human retina.
PURPOSE: In addition to acting as an optical filter,
macular (carotenoid) pigment has been hypothesized to function
as an antioxidant in the human retina by inhibiting the
peroxidation of long-chain polyunsaturated fatty acids.
However, at its location of highest density in the inner
(prereceptoral) layers of the foveal retina, a specific
requirement for antioxidant protection would not be predicted.
The purpose of this study was to determine whether lutein and
zeaxanthin, the major carotenoids comprising the macular
pigment, are present in rod outer segment (ROS) membranes
where the concentration of long-chain polyunsaturated fatty
acids, and susceptibility to oxidation, is highest. METHODS:
Retinas from human donor eyes were dissected to obtain two
regions: an annular ring of 1.5- to 4-mm eccentricity
representing the area centralis excluding the fovea
(perifoveal retina) and the remaining retina outside this
region (peripheral retina). ROS and residual (ROS-depleted)
retinal membranes were isolated from these regions by
differential centrifugation and their purity checked by
polyacrylamide gel electrophoresis and fatty acid analysis.
Lutein and zeaxanthin were analyzed by high-performance liquid
chromatography and their concentrations expressed relative to
membrane protein. Preparation of membranes and analysis of
carotenoids were performed in parallel on bovine retinas for
comparison to a nonprimate species. Carotenoid concentrations
were also determined for retinal pigment epithelium harvested
from human eyes. RESULTS: ROS membranes prepared from
perifoveal and peripheral regions of human retina were found
to be of high purity as indicated by the presence of a dense
opsin band on protein gels. Fatty acid analysis of human ROS
membranes showed a characteristic enrichment of
docosahexaenoic acid relative to residual membranes. Membranes
prepared from bovine retinas had protein profiles and fatty
acid composition similar to those from human retinas.
Carotenoid analysis showed that lutein and zeaxanthin were
present in ROS and residual human retinal membranes. The
combined concentration of lutein plus zeaxanthin was 70%
higher in human ROS than in residual membranes. Lutein plus
zeaxanthin in human ROS membranes was 2.7 times more
concentrated in the perifoveal than the peripheral retinal
region. Lutein and zeaxanthin were consistently detected in
human retinal pigment epithelium at relatively low
concentrations. CONCLUSIONS: The presence of lutein and
zeaxanthin in human ROS membranes raises the possibility that
they function as antioxidants in this cell compartment. The
finding of a higher concentration of these carotenoids in ROS
of the perifoveal retina lends support to their proposed
protective role in age-related macular degeneration.
Invest Ophthalmol Vis Sci 2000
Apr;41(5):1200-9
The role of oxidative stress in the
pathogenesis of age-related macular degeneration.
Age-related macular degeneration (AMD) is the leading cause
of blind registration in the developed world, and yet its
pathogenesis remains poorly understood. Oxidative stress,
which refers to cellular damage caused by reactive oxygen
intermediates (ROI), has been implicated in many disease
processes, especially age-related disorders. ROIs include free
radicals, hydrogen peroxide, and singlet oxygen, and they are
often the byproducts of oxygen metabolism. The retina is
particularly susceptible to oxidative stress because of its
high consumption of oxygen, its high proportion of
polyunsaturated fatty acids, and its exposure to visible
light. In vitro studies have consistently shown that
photochemical retinal injury is attributable to oxidative
stress and that the antioxidant vitamins A, C, and E protect
against this type of injury. Furthermore, there is strong
evidence suggesting that lipofuscin is derived, at least in
part, from oxidatively damaged photoreceptor outer segments
and that it is itself a photoreactive substance. However, the
relationships between dietary and serum levels of the
antioxidant vitamins and age-related macular disease are less
clear, although a protective effect of high plasma
concentrations of alpha-tocopherol has been convincingly
demonstrated. Macular pigment is also believed to limit
retinal oxidative damage by absorbing incoming blue light
and/or quenching ROIs. Many putative risk-factors for AMD have
been linked to a lack of macular pigment, including female
gender, lens density, tobacco use, light iris color and
reduced visual sensitivity. Moreover, the Eye Disease
Case-Control Study found that high plasma levels of lutein and
zeaxanthin were associated with reduced risk of neovascular
AMD. The concept that AMD can be attributed to cumulative
oxidative stress is enticing, but remains unproven. With a
view to reducing oxidative damage, the effect of nutritional
antioxidant supplements on the onset and natural course of
age-related macular disease is currently being evaluated.
Surv Ophthalmol 2000
Sep-Oct;45(2):115-34
Protein oxidation and loss of protease
activity may lead to cataract formation in the aged lens.
Over 95% of the dry mass of the eye lens consists of
specialized proteins called crystallins. Aged lenses are
subject to cataract formation, in which damage, cross-linking,
and precipitation of crystallins contribute to a loss of lens
clarity. Cataract is one of the major causes of blindness, and
it is estimated that over 50,000,000 people suffer from this
disability. Damage to lens crystallins appears to be largely
attributable to the effects of UV radiation and/or various
active oxygen species (oxygen radicals, 1O2, H2O2, etc.).
Photooxidative damage to lens crystallins is normally retarded
by a series of antioxidant enzymes and compounds. Crystallins
which experience mild oxidative damage are rapidly degraded by
a system of lenticular proteases. However, extensive oxidation
and cross-linking severely decrease proteolytic susceptibility
of lens crystallins. Thus, in the young lens the combination
of antioxidants and proteases serves to prevent crystallin
damage and precipitation in cataract formation. The aged lens,
however, exhibits diminished antioxidant capacity and
decreased proteolytic capabilities. The loss of proteolytic
activity may actually be partially attributable to oxidative
damage which proteases (like any other protein) can sustain.
We propose that the rate of crystallin damage increases as
antioxidant capacity declines with age. The lower protease
activity of aged lens cells may be insufficient to cope with
such rates of crystallin damage, and denatured crystallins may
begin to accumulate. As the concentration of oxidatively
denatured crystallins rises, cross-linking reactions may
produce insoluble aggregates which are refractive to protease
digestion. Such a scheme could explain many events which are
known to contribute to cataract formation, as well as several
which have appeared to be unrelated.
Free Radic Biol Med
1987;3(6):371-7
Macular pigment optical density in a
midwestern sample.
OBJECTIVE: To assess the distribution of the macular
pigments (MPs) lutein (L) and zeaxanthin (Z) in a healthy
sample more representative of the general population than past
studies and to determine which dietary factors and personal
characteristics might explain the large interindividual
differences in the density of these MPs. DESIGN: Prevalence
study in a self-selected population. PARTICIPANTS: Two hundred
eighty healthy adult volunteers, consisting of 138 men and 142
women, between the ages of 18 and 50 years, recruited from the
general population. METHODS: MP optical density was measured
psychophysically at 460 nm by use of a 1 degrees test field.
Serum was analyzed for carotenoid and vitamin E content with
reversed-phase high-performance liquid chromatography. Usual
intakes of nutrients over the past year were determined by
means of a food frequency questionnaire. MAIN OUTCOME
MEASURES: MP optical density. RESULTS: Mean MP optical density
measured 0.211 +/- 0.13, which is approximately 40% lower than
the average reported in smaller, less representative studies.
MP density was 44% lower in the bottom versus the top quintile
of serum L and Z concentrations. Similarly, MP density was 33%
lower in the bottom compared with the top quintile of L and Z
intake. MP density was 19% lower in blue-grey-eyed subjects
than in subjects with brown-black irises. When all variables
were considered together in a general linear model of
determinants of MP, statistically significant (P < 0.05)
relationships were found between MP density and serum L and Z,
dietary L and Z intake, fiber intake, and iris color.
CONCLUSIONS: These data suggest that MP values in this healthy
adult population are lower than in smaller select samples.
Moreover, these data indicate that MP is related to serum L
and Z, dietary L and Z intake, fiber intake, and iris
color.
Ophthalmology 2001
Apr;108(4):730-7
The potential role of dietary
xanthophylls in cataract and age-related macular
degeneration.
The carotenoid xanthophylls, lutein and zeaxanthin,
accumulate in the eye lens and macular region of the retina.
Lutein and zeaxanthin concentrations in the macula are greater
than those found in plasma and other tissues. A relationship
between macular pigment optical density, a marker of lutein
and zeaxanthin concentration in the macula, and lens optical
density, an antecedent of cataractous changes, has been
suggested. The xanthophylls may act to protect the eye from
ultraviolet phototoxicity via quenching reactive oxygen
species and/or other mechanisms. Some observational studies
have shown that generous intakes of lutein and zeaxanthin,
particularly from certain xanthophyll-rich foods like spinach,
broccoli and eggs, are associated with a significant reduction
in the risk for cataract (up to 20%) and for age-related
macular degeneration (up to 40%). While the pathophysiology of
cataract and age-related macular degeneration is complex and
contains both environmental and genetic components, research
studies suggest dietary factors including antioxidant vitamins
and xanthophylls may contribute to a reduction in the risk of
these degenerative eye diseases. Further research is necessary
to confirm these observations.
J Am Coll Nutr 2000 Oct;19(5
Suppl):522S-527S
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