1
IES LAS MUSAS
TRABAJO DE INVESTIGACIÓN
LUTEIN AND ZEAXANTHIN AS
PROTECTORS AGAINST AGE RELATED
MACULAR DEGENERATION
Authors: Lorena Rodríguez Bravo and Bárbara Rodríguez Sarrión
Tutors: J. Carlos Ortega Lázaro and Mª Elvira López-Oliva Muñoz
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INDEX
Appreciations ............................................................................................................................... 3
Personal motivation ...................................................................................................................... 3
Objectives .................................................................................................................................... 3
Abstract ........................................................................................................................................ 4
Introduction .................................................................................................................................. 5
Eye anatomy................................................................................................................................. 5
Age-Related Macular Degeneration ........................................................................................... 15
Causes ................................................................................................................................ 15
Symptoms .......................................................................................................................... 16
Diagnosis ........................................................................................................................... 16
Risk factors ........................................................................................................................ 20
Treatment ........................................................................................................................... 21
Prevention .......................................................................................................................... 22
Macular pigments; Lutein and Zeaxanthin ................................................................................. 23
Functions ................................................................................................................................ 23
Roles in visual health ............................................................................................................. 24
Dietary sources ....................................................................................................................... 26
Measurement .......................................................................................................................... 27
Absorption .............................................................................................................................. 27
Transport and tissue distribution ............................................................................................ 28
Roles in Age-Related Macular Degeneration ......................................................................... 28
Recommended intake values ................................................................................................. 29
Conclusion ................................................................................................................................. 30
Lecture cited............................................................................................................................... 31
3
APPRECIATION This work would not have been possible without the help of several people. We would like to
thank our inner tutor of the project, Carlos Ortega for helping and guiding us throughout the
whole investigation of this project and our English teacher, Mª Ángeles Martín Llantino, for
helping us to express our research in the language of English. We want to show our gratitude as
well to Maria Elvira López Muñoz, our external tutor and teacher in the Pharmacy faculty of the
Complutense University of Madrid for her involvement in the project. Her help, dedication and
experience have been essential in the development of this study. Moreover, we would like to
stand out the task of the Complutense University of Madrid for allowing us to work there and
live such a satisfying experience. To sum up, we would like to thank the high school IES Las
Musas for all the effort made to give us the opportunity to work and research on such an
interesting project.
PERSONAL MOTIVATION One of the main reasons we have carried out this work is because of the desire of doing
something different in Bachillerato. We certainly believe that the investigation projects are
highly beneficial for the students, as they are given the chance of working in a more practical
and professional way on something that causes us curiosity. Furthermore, this project will
prepare us for the future and therefore we will be able to face better this kind of works.
Personally, we have been interested in the human eye for a long time and when we saw we
could investigate and increase our knowledge of this organ we did not hesitate. As our external
tutor is an expert of nutrients, we decided that it could be interesting to unite her knowledge and
our passion about the eye and we came up with the idea of investigating the role of some
antioxidants against a very serious ocular disease which is the Age-Related Macular
Degeneration.
OBJECTIVES There are several aims to be accomplished in this project. First of all, it is necessary the
acquisition of the knowledge of ocular anatomy, Age- Related Macular Degeneration, Lutein
and Zeaxanthin. Afterwards, the information learned before will be used to fulfill the main
objective of this study which is the analysis of the roles of Lutein and Zeaxanthin. In the case
they are beneficial for the eye, the intake values recommended will be calculated in order to
improve the condition of all the people who have AMD.
4
Abstract: The retina is a light sensitive tissue whose central part is the macula, the main part
of our vision camp. There is an ocular disease called Age Related Macular Degeneration(AMD)
which produces visual disturbances as it gradually destroys the macula. This sickness is so
aggressive that is the leading cause of vision loss in people over 60 years old. This disease has
two types; the Dry AMD, provoked by the accumulation of extracellular metabolism waste
products in the macula, called drusen and the Wet AMD caused by the abnormal growth of new
blood vessels behind the macula. While the Wet AMD is treated with laser technology, the Dry
AMD has no specific treatment, but a nutritional therapy. It has been suggested that the addition
of antioxidants like Lutein and Zeaxanthin may have some protective effect for the eye against
the AMD. L and Z are antioxidants that form the macular pigment(MP), a region of the macula
responsible for fine-feature vision. In this study, it will be analyzed if a nutritional
supplementation with L and Z has a positive effect in people with AMD and if it protects people
who does not have this ocular disorder.
Resumen: La retina es un tejido sensible a la luz cuya parte central es la mácula, el centro de
nuestro campo visual. Existe una enfermedad ocular llamada Degeneración Macular asociada a
la Edad (DME) que produce alteraciones visuales a medida que gradualmente va destruyendo la
mácula. Esta enfermedad es tan agresiva que es la principal causa de la pérdida de visión en
personas de más de 60 años. Esta enfermedad tiene dos tipos; la DME seca, la cual está
provocada por la acumulación de productos de desecho del metabolismo extracelular llamados
drusas y la DME húmeda, causada por el crecimiento anormal de nuevos vasos sanguíneos por
detrás de la mácula. Mientras que la DME húmeda es tratada con tecnología láser, la DME seca
no tiene ningún tratamiento específico excepto una terapia nutricional. Se ha planteado el hecho
de que la adición de unos antioxidantes llamados, Luteína(L) y Zeaxantina(Z), pueda tener un
efecto protector para el ojo frente a la DME. La L y Z son antioxidantes que forman el pigmento
macular(PM), una región de la mácula que es responsable de la visión en detalle. En este
estudio, se analizará si una suplementación nutricional con L y Z tiene un efecto positivo en
personas con DME y si protege a las personas que no tienen esta enfermedad ocular.
5
INTRODUCTION
It is known that the eye is the main organ of the sense of sight, that receives the pictures of what
we are seeing and it transforms them into electric signs which go through the optic nerve to the
brain. There, after these electric signs are interpreted, we receive the information about the
things we are looking at. The eye is a complex organ whose correct functioning depends on the
collaboration of its multiple parts. In particular, the retina is a light sensitive tissue responsible
for the image formation processing and its central part, the macula is essential for the fine-
feature vision. Any kind of alteration in the retina can have serious consequences like in the
Age-Related Macular Degeneration as we will see later.
ANATOMY OF THE EYE
It is known that the eye is the main organ of the sense of sight, that receives the pictures of what
we are seeing and it transforms them into electric signs which go through the optic nerve to the
brain. There, after these electric signs are interpreted, we receive the information about the
things we are looking at.
The eye is a sphere, approximately 25 mm in diameter with a weight of 8 grams. The eye lies in
the bony orbit of the skull. Anatomically, the eye can be divided in two compartments, the
anterior segment (including the cornea, iris, lens, anterior and posterior chamber) and the
posterior segment (the remainder of the eye).
The eye contains a huge number of factors that protect it from any damage. One of these, is a
regulated complement system that is continuously activated protecting some compartments of
the eye. Another example, is the multiple blood-ocular barriers formed by tight junctions in the
uvea, the endothelial cells of the capillaries located in the retina and the cornea. Therefore, if
these ocular barriers are broken or downregulated, the eye becomes really vulnerable to any
attack, for instance, the invasion of non-resident immune cells which can cause tissue damage.
[1]
Moreover, the eye has several functional layers, which can be divided in this way:
6
Cornea: it is an avascular and transparent protective barrier that covers the anterior
ocular surface. It is about 0.5 mm in thickness and protects the eye against infections
and injuries. However, its main purpose is to transmit and focus light into the eye. The
external surface of the cornea is covered by a tear film , and the internal is in contact
with the aqueous humor. This is a transparent liquid whose function is to nourish the
cornea. Moreover, the cornea can be divided into five main layers, which are; the
corneal epithelium (the most superficial layer), the Bowman’s layer, the corneal stroma
Figure 1
7
(constituting 90% of the cornea), the Descemet’s layer and the corneal endothelium (the
most internal layer). [1]
Limbus: the corneal edge or limbus, is a band that encircles the peripheral cornea. It is
a transitional zone between the cornea and the sclera, and the cornea and the
conjunctiva. It is formed by cells derived from its adjacent tissues. In addition, the stem
cells of the limbus maintain and renew the corneal epithelium cell layers. [1]
Sclera: this is a white opaque collagen-enriched layer that helps to maintain the shape
of the eye, and the muscles attached to it, control the movements of the eye. This layer
is known as the “white of the eye”. [1]
Figure 4
Figure 5
Figure 3
Figure 2
8
Conjunctiva: it is a thin, translucent, vascularized mucus secreting membrane. It can
be divided into the bulbar area (on the eye surface) and the palpebral area (lining the
posterior surface of the eyelids). The superficial conjunctival epithelium has mucin-
producing goblet cells, which in combination with lymphoid cells and resident T-cells,
have an important role in the ocular defense and immunological protection of the tear
film. [1]
The lens: the lens is called crystalline. It consists of stiff, elongated, prismatic cells
tightly packed together. It is biconvex and it is attached to the ciliary process by zonular
fibers called, Zinn’s zonulas. Moreover, the crystalline is avascular, colourless and
transparent and its mission is to focus the light rays on the retina. [1]
In addition, through a process called accommodation, we are able to focus on objects
located at different distances, as the curvature of the lens is modified due to the
contractions od the ciliary muscle. Therefore, as we can see in the picture, the light from
a distant object, and from a nearby object, strikes in the same point of the retina thanks
to the modification of the curvature of the lens .[1]
Figure 6
Figure 7
9
Iris: this is a highly vascularized, coloured, smooth muscle portion of the uvea, located
between the cornea and the crystalline with the pupil in its center. It divides the anterior
segment into posterior and anterior chambers. The colour of the iris depends of the
amount and the distribution of melanin. The iris is responsible for regulating the amount
of light that enters into the eye, through the sphincter muscle of the pupil, which adapts
to the intensity of light. In this way, when the light is intense, the pupil contracts
(miosis) in order to reduce the light that enters in the eye. On the contrary, when light is
scarce, the pupil dilates (mydriasis) to capture the maximum possible light. [1]
Ciliary body: this is a structure formed by melanocytes, muscle cells, fibroblasts,
epithelium and pigmented epithelial cells and it is the anterior continuation of the
choroid and retina. It is responsible for the thickness of the lens and its curvature during
the process explained before called accommodation. [1]
Figure 9
Figure 10
Figure 8
10
Choroid: it is a highly vascular layer located between the sclera and the retina. Its
structure can be divided into Bruch’s membrane( the most internal layer), the choroidal
stroma, the network of the choriocapillaris, and the outer suprachoriod lamina. The
choroid, is responsible for regulating the retinal temperature and the exchange of
catabolites, fluids, nutrients, oxygen, and blood between the choroid and the retina. [1]
Vitreous humor: this is a transparent gel placed behind the lens occupying most of
the inside of the eye and it is also in contact with the retina. Anatomically, it can be
divided into the central vitreous, the basal vitreous, the vitreous cortex, the vitreoretinal
interface and the zonule. It is composed by 98% of water and 2% of collagen fibrils and
its mission is to help the eye maintain its shape.[1]
Figure 11
Figure 12
11
Retina: it is a light sensitive tissue located on the inner surface of the eye. The light
that hits the retina, produces various chemical and electric phenomena which are
translated into nerve impulses that are subsequently sent to the brain through the optic
nerve. [2]
The retina can be divided into some macroscopic parts:
o Papilla or optical disc: it is a pink disc approximately 2x1.5 mm. The optic
nerve going through this disc and therefore, going through the sclera, choroid
and retina is able to enter into the eyeball. As the optical disc does not receive
any light, it does not have any photoreceptors, and as a result it is considered a
blind spot.
o Fovea: this is a small structure placed in the center of the retina and surrounded
by the macula. The fovea is responsible for detailed vision.
o Ora serrata: it is the most anterior and peripheral portion of the retina, and it is
in contact with the ciliary body.
o Macula: this is the central area of the retina, and it surrounds the fovea.
o Peripheral retinal area: this zone has less activity of photoreception, as it has
less photoreceptors.
Figure 13
12
On the microscopic structure of the retina, we find ten parallel layers which are:
o Retinal pigment epithelium: it is a monolayer of hexagonal cells which have
pigment, especially, melanin granules and it is located in the outside of the
retina. It is anchored to the choroid, specifically to the Bruch’s membrane. It
has many functions, such as, nourish the photoreceptors and the maintenance of
retinal adhesion, light adsorption, phagocytosis of the outer segments of the
photoreceptors, relying on nutrition from the choroidal blood flow to the retina
and the participation in the blood-retina barrier. [5]
o Layer of photoreceptor cells: it consists of the extremes of the segments of the
photoreceptors.
o Outer limiting layer: it is a group of intercellular junctions between the cells
photoreceptors and the Muller cells.
o Nuclear layer or granular external: it is composed by the nuclei of the cons and
rods.
Figure 14
Figure 15
13
o Outer plexiform layer: it is the region of the synaptic connection between cells
photoreceptors and bipolar cells.
o Nuclear layer or granular internal layer: it is formed by the nuclei of the bipolar
cells, horizontal cells and amacrine cells.
o Inner plexiform layer: this is the area of the synaptic connection between
bipolar cells , amacrine cells and ganglion cells.
o Layer of ganglion cells: it is composed by the nuclei og the ganglion cells.
o Optic nerve fiber layer: it is formed by the axons of the ganglion cells that also
form the optic nerve.
o Inner limiting layer: this is the layer which separates the retina from the
vitreous humor. [2]
The retina has three types of cells:
o Pigmented cells: they are responsible for the metabolism of the photoreceptors.
o Neurons:
- Photoreceptor cells: they are the cons and rods. They transform the
light into electric signals. The human retina has 6.5 million cones and
120 million rods. The rods work in low light conditions and provide the
vision in black and white. On the contrary, the cones are adapted to
situations with great
luminosity and they provide
the color vision. [3]
Figure 16 Figure 17
14
- Bipolar cells: of the retina: they connect the photoreceptors with the
ganglion cells.
- Amacrine cells and horizontal cells: they are modulating interneurons.
- Ganglion cells: the optic nerve goes from these cells to the retina and
then to the brain.
o Supportive cells:
- Astrocytes: they sheath superficial blood vessels in the inner retina.
- Muller cells: they are essential for maintaining the cellular micro-
environment and the stability of the entire retinal sheet. [4]
Optic nerve: it is the second cranial nerve that starts in the optic nerve head and
reaches the brain. As we know, the light is captured by the photoreceptors, as it enters
into eye and it is reflected in the retina thanks to the accommodation. Then, the light is
transformed into electric signs that are transported to the visual cortex in the brain by
the optic nerve. There, they will be analyzed and we will receive the information about
what we are seeing. [5]
Figure 18
15
AGE-RELATED MACULAR DEGENERATION
Age-Related Macular Degeneration (AMD) is the leading cause of vision loss in people over 60
years old. It is a chronic ocular disorder that produces visual disturbances as it affects the
macula, which is the central part of the retina and it is the main part of our vision field. [6]
Causes: its origin may be due to multiple factors. There are two types of AMD:
o Dry AMD: it is the common one. In this type, a series of extracellular
metabolism waste products called drusen accumulates under the retina, between
the retinal pigmentary epithelium (RPE) and the Bruch membrane. As time
goes by, the drusen gradually alter the RPE causing not only its death but also
the loss of the photoreceptors in the retina, the cones and rods. This leads to
vision becoming more and more blurred until it is lost in its entirety. It has three
stages;
- Early AMD: in this phase, patients have some small or medium-sized
drusen, however there is no vision loss.
- Middle AMD: in this case, patients have many medium-sized drusen or
few large drusen, causing sometimes, the appearance of a big blurred
spot in the centre of the visual field. Moreover, in this phase, some
patients may need more light for tasks like reading.
- Advanced AMD: at this stage, patients have a large number of drusen
and their RPE , their photoreceptors and their retinal supporting tissues
are broken. Furthermore, a large blurred spot appears in the centre of
the visual field (the macula) and with the passage of time, it can
increase its size and get darker. All this causes a total loss of the central
vision in the long term. [7]
Figure 19 Figure 20
16
o Wet AMD: it is produced when blood vessels grow behind the macula as the
RPE and the photoreceptors are dying. Firstly, the Bruch membrane starts to
break near the drusen and new blood vessels are formed and they start to grow.
This growth is known as neo-vascularization. The new blood vessels are really
fragile and they start leaking liquid and blood which turns out in the
cicatrisation of the macula. Moreover, this causes permanent damage to the
photoreceptors, which die and create blind spots in the retina. In this way,
straight vision can be distorted or lost in its entirety during a brief period of
time, sometimes days or weeks. This type represents 10% of the cases of AMD.
It does not have any stages, since this sort of AMD is considered advanced. [7]
Symptoms: in the early stages of AMD, symptoms may not be detected. The first sign
usually noticed is a gradual or sudden alteration in the quality of the vision. Dark, blurry
spots or straight lines might appear causing the deterioration of the visual ability.
However, all these signs may not be caused by this disease, therefore, the patient must
go to the doctor to analyse the visual problem and to be given a diagnosis.[8]
Diagnosis: as we know, the first stages of AMD usually start without symptoms,
therefore, only an eye exam can detect this disease. The exam may be formed by
different test, some of them are:
o Visual acuity test: in order to measure the visual ability from different
distances. [9]
Figure 21 Figure 22
17
o Dilated eye exam: the ophthalmologist puts eye drops in the patients eyes to
dilate the pupils to have a better view of the back of the eye. Then using a
special magnifying lens, the ophthalmologist examines the retina and the optic
nerve for signs of AMD and other eye problems. With this process the dry
AMD can be detected, and if it is so, the patient may have to try the Amsler
grid next to check for macular degeneration symptoms and therefore, confirm
the diagnosis.
As we know, the pupils, open wide allowing the ophthalmologist to see the
retina, the optic nerve and the macula, for instance (Figure 7). If the patient had
AMD, the doctor would see yellow spots beneath the retina which are known as
drusen. (Figure 8) This would mean the patient has dry AMD. [9]
Figures 24 and 25
Figure 27
Figure 26
Figure 23
18
o Amsler grid: this is a pattern of straight black horizontal and vertical lines that
form multiples white squares. If the patient sees some wavy lines instead of
straight lines or if some of the lines are missing for the patient, it could be a
sign of AMD. [10]
o Optical coherence tomography(OCT): this device is used for obtaining 3D high
resolution images of the retina, which allows the ophthalmologist to analyse the
state of the retina parts. This process is similar to ultrasound technology except,
the image is performed by light instead of sound. [11]
o F
Figure 28
Figure 31
Figure 29 Figure 30
19
luorescein angiography: in this procedure, the ophthalmologist injects a dye
into a vein of the patient’s arm. Afterwards, when the dye has reached the eye
and flowed through the blood vessels of the retina, the doctor takes some
photographs. In this way, the resultant images are able to show new vessels or
vessels that are leaking fluid or blood in the macula, which is the cause of wet
AMD. [10]
Figure 33
Figure 34
Eye with
Wet AMD Other case of Wet
AMD
Figure 32
20
Risk factors:
o Advanced age: although AMD may occur earlier, the risk of this disease
increases with age. Therefore, people over 60 are at greater risk than those who
are younger. [12]
o Race: AMD is more prevalent in the Caucasian population than in other races
with more darkly pigmented skin, hair and eye color. Therefore, Europeans are
more likely to develop AMD than Africans, Asians, and Hispanics. [13]
o Gender: it is known that women are statistically more likely to develop AMD,
however some studies, such as the Beaver Damn Eye Study, the Blue
Mountains Eye Study and the Rotterdam Study revealed that there are not any
differences between genres in relation to AMD risk. [13]
o Family History: this disease has multiple inherited risk factors, including one
major genetic risk locus on chromosome 1, along with other minor genetic risk
factors. [13]
o Cigarette smoking: smoking increases the possibilities of having AMD, as the
retina has a high rate of oxygen consumption, anything that affects the oxygen
delivery, causes damage to the vision. Moreover, smoking causes oxidative
damage, which contributes to the progression of this disease. [14]
o Oxidative stress: this refers to cellular damage caused by reactive oxygen
species (ROS), which have free radicals, peroxides and other products from the
oxygen metabolism. As time goes by, the RPE, accumulates lipofuscin which
acts as a photosensitizer, generating ROS. The problem is that the retina is
really susceptible to oxidative stress because of its high oxygen consumption
and the high exposure to light. As we age, the oxidative damage increases and
the antioxidant capacity to stop this damage decreases. It is believed that these
oxidative age-related changes indicate an early AMD, which, in combination
with heredity susceptibility and other retinal modifiers, can turn out into the
advanced AMD. Later on, some antioxidants such as lutein and zeaxanthin will
be studied in order to see if they can reduce oxidative damage and therefore the
risk of AMD. [13]
21
o Excessive light exposure: it can be an AMD risk factor, since it aggravates
oxidative damage. [13]
o Diet: people whose diets are elevated in fat, cholesterol and high- glycemic
index foods, and low in antioxidants and green leafy vegetables may be more
likely to develop AMD. However, low-glycemic diets can lower the risk of
AMD by stabilizing blood sugar levels. [14]
o High blood pressure: this leads to the narrowing of the blood vessels that
nourish the retina and therefore, it causes the restriction of the oxygen flow.
[14]
o Inactivity: in dry AMD the retina does not receive adequate oxygen, leading to
the death of cells of the RPE. In this case, exercise may help, as it improves
cardiovascular health. [14]
Treatment
o Dry AMD: the treatment for this type of AMD is based on a nutritional therapy.
According to the patient’s condition, supplements will be prescribed in order to
add the quantities needed of certain vitamins, minerals and antioxidants to
increase healthy pigments and support the cell structure.[15].
o Wet AMD: there are multiple techniques to treat this form of AMD;
- Anti-VEGF (vascular endothelial growth factor) Therapy : nowadays, it
is the most effective treatment for wet AMD. It is a periodic intravitreal
injection of “anti-VEGF”. VEGF is a molecule that is made by the RPE
and it supports the growth of new blood vessels, so it is healthy for our
body. Nevertheless, in the case of macular health , this molecule
promotes the growth of new, weak blood vessels in the choroid which
start leaking blood, lipids and serum into the retinal layers, and this
leads to the death of the RPE and the photoreceptors. In this way, an
intraocular injection of “anti-VEGF” drugs inhibits the formation of
the new blood vessels and may avoid the leakage. The effect usually
lasts for about a month. High rates of success with anti-VEGF
injections have been reported, including, receding blood vessels behind
22
the retina, a slower development of the disease, and in some patients,
improvements in vision capacity. [16]
- Laser therapy: in this method, the pupil is dilated using drops and an
anesthetic is given to numb the surface of the eye and in some cases to
keep the eye from moving. Afterwards, a high-energy laser beam is
aimed at the leaking blood vessels in order to seal them and to stop
them from growing. Depending on how close the abnormal vessels are
to the center of the macula, the patient may experience some permanent
blurring. Usually the patient needs a retreatment after four years. [15]
- Photodynamic Therapy (PDT): this technique is based on two steps.
Firstly, a drug called “Visudyne” is injected intravenously into the
patient’s arm in order to help direct the laser to the affected area. It
travels to the abnormal vessels which are causing the wet AMD. Then,
the drug is activated by shining a low energy non-thermal laser light
and this leads to the destruction of the unwanted leaking vessels. This
procedure seals off the leaking vessels while leaving the healthy ones
intact. This technique needs to be applied multiple times to complete
the treatment. [16]
Prevention: there are many ways that may help protect vision and reduce the risk of
developing AMD.
o Do not smoke.
o Take a balanced diet that includes green leafy vegetables, yellow and orange
fruit and fish.
o Take a balanced multivitamin supplement.
o Do exercise regularly.
o Keep the blood pressure and the levels of cholesterol under control.
o Avoid long sun exposure.
o Wear sunglasses to block UV and blue light that may cause eye damage.
o Have regular eye exam.
[17]
23
MACULAR PIGMENTS; LUTEIN AND ZEAXANTHIN
As we know one of the causes of AMD is the oxidative stress in the retina. Current evidence
suggests that some supplements such as lutein and zeaxanthin, as they are antioxidants, they
have a protective effect by reducing this stress and therefore they contribute to the improvement
of people with AMD.
Lutein (L) and zeaxanthin (Z) are two antioxidants that belong to the class of carotenoids called
xanthophylls. L, Z and their isomer called meso-zeaxanthin(MZ) form the macular pigment
(MP) which is a region of the macula that is responsible for fine-feature vision. There are
between 20 and 30 carotenoids in the human body, however, only L ,Z, and MZ are in the eye,
specifically, in the macula. [18]
MZ is the dominant carotenoid at central part of the macula (the fovea) and the radio of Z to L
declines and concentration of Z decreases with increasing the distance away from the fovea. In
this way, MZ is the dominant carotenoid at the central part, Z at the mid-periphery and L at the
periphery of the macula. [19]
FUNCTIONS
These carotenoids carry out some functions such as:
Light absorption: L and Z absorb between 40-90% of blue light, reducing the light
scatter and protecting indirectly this way the retina from oxidative damage. They act as
an internal sunglasses preventing the blue light from reaching the photoreceptors of the
retina, the cons and rods. However, the 78% of the population of USA for example,
does not have the optimal MP to protect the eye from this light. And as a result, it is
Figure 35
24
common to take supplements of L and Z in the diet, to help the MP protect the retina.
[19,20]
Protection against inflammation: L protects the eye from inflammation, which is a
pathogenic mechanism that can affect many regions in the eye and it appears in order to
prevent the increase of oxidation induced cytokines for instance. Moreover, L reduces
systemic inflammation by decreasing factor D(an enzyme that activates inflammation).
[21]
Oher functions: some evidence suggests that these carotenoids may play an important
role in cell-to-cell communication and the presence of L and Z in the neural retina and
brain may improve the transmission of visual impulses to the brain. [21]
ROLES IN VISUAL HEALTH
These antioxidants also contribute enhancing visual performance.
Visual acuity: this is the ability to resolve objects that are in high contrasts to their
background. It is measured by the ability to recognize small letters at a certain distance.
Some studies prove that there are improvements in visual acuity when L and/or Z are
supplemented alone or with other antioxidants. Furthermore, these upgrades have been
found even in people with early or advanced AMD, or with diabetic retinopathy and not
only has improved visual acuity but also L and Z have had an protective effect. Besides,
Figure 36
25
apart from the improvement in visual acuity caused by the MP in indoors test, it can
help us see further . It is believed that a person with 1.0 density unit of MP can see 26%
further than someone with little or no MP. [22]
Contrast sensitivity: it is the ability to recognize contrasts in levels of lightness and
darkness between certain objects and the background. This is correlated with orientation
and mobility, reading speed and driving. People who have been taking supplements that
contain L and Z, for three months to three years, have improved contrast sensitivity .
Among these individuals, some of them are young and healthy, others have early or
advanced AMD or diabetes but all of them have been benefited. Besides, L and Z,
protect the eye from age- and disease-related changes in long terms. [22]
Photo stress recovery and glare reduction: high levels of MP help the eye by:
o Reducing the impact of bright light as it reduces the time needed to recover
from it.
o Enhancing the ability to see in conditions of glare.
o Enhancing visual performance as it increases the range over which vision task
can be comfortably performed.
Therefore, the supplementation of L and Z helps on glare disability. [22]
Visual processing speed: as we know, the light captured by the photoreceptors is
transformed into electric signs that are transported through the optic nerve to the visual
cortex of the brain. There, it will be interpreted and we will receive the information
about what we are seeing. Some studies have revealed the possibility that high MP
levels based on the supplementation of L and Z, may improve visual processing speed.
[22]
Dark adaptation: it has been studied the possibility that MP may protect against
impairments in rod dark adaptation, which is essential for the contrast sensitivity. These
impairments occur because of the accumulation of hydrophobic lipids in the RPE,
which creates a barrier that slows the delivery of nutrients to rods, provoking they do
not work efficiency. [22]
26
DIETARY SOURCES OF LUTEIN AND ZEAXANTHIN In the beginning, L and Z were measured together because the techniques were not able to
separate the quantification of each carotenoids in an individual way. As we can see in the table,
vegetables sources contain only L, whereas corn and eggs contain both, L and Z.
Nowadays, the L and Z content has been individually studied. Moreover, some studies
revealed the possibility that MZ may be present in small amounts I the food supply, for
example in the egg yolk.
Figure 37
Figure 38
27
The availability of carotenoids from different type of food allows having a more varied and
easily maintainable diet. [23]
MEASUREMENT There are several techniques to measure L and Z. Most of them use the unit of “optical density”
that is equivalent to 0.025 ng MP over a 1mm^2 area of retinal tissue.
The levels of L and Z vary in each person which makes dietary, metabolic and genetic
differences on L and Z absorption, transport in blood and accumulation in the eye. Dietary
supplementation containing L and Z has been given for 6 to 24 months to individuals whose
macular pigment optical density (MPOD)has been increased but in different quantities. It is
believed that there are many influences on the uptake, transport, and retinal capture of L and Z
which provokes those differences. [24]
ABSORPTION It varies according to the food preparation methods, the bioavailability of L and Z and the
proteins that absorb these carotenoids. Consuming aliments with high concentration of L and Z
increases blood response. These antioxidants are more available in aliments like eggs and many
types of brightly coloured fruits and vegetables typical of a western diet. [25]
However, the bioavailability also depends on the proteins that influence the cholesterol uptake
into the intestinal lumen, because L is transported by cholesterol transporter proteins. Once L is
in the intestinal lumen, these proteins modulates the uptake of L and Z. Moreover, the
absorption of L and Z depends on the intake of beta-carotene and the activity of the enzyme
beta-carotene oxygenase 1(BCO1). The availability of these components in the diets reduces
the absorption of L and Z, as we can see in a recent trial. In this study, adding L and Z to a high
dose of antioxidant that contained beta-carotene did not lower the AMD progression, except in
individuals who took a supplementation without beta-carotene. Besides, five years later, the
levels of L and Z were higher in people who did not take beta-carotene than people who did.
Therefore, with this experiment, it has been verified that beta-carotene reduces the absorption of
L and Z, their levels in the organism and as a result, these low levels of L and Z were obviously
not effective enough to protect the eye from AMD in people who take beta-carotene. [26]
28
TRANSPORT AND TISSUE DISTRIBUTION
L and Z are transported by the secretion of the enterocytes in chylomicrons who take them to
the liver. There, they are repackaged into lipoproteins and then they are distributed throughout
the body.
Carotenoids are stored in a tissue called, adipose tissue. Nevertheless, their distribution in this
tissue varies depending on the metabolic status of the individuals. For instance, obesity and
diabetes are associated with lower levels of serum carotenoids and lower MPOD. In addition,
there is an inverse relationship between MPOD and metabolic syndrome phenotypes. There are
three possible explanations for lower levels of L and Z in serum and MPOD in people with
those phenotypes. As they are associated with high oxidative stress and inflammation, the
turnover of carotenoids may vary. The second is reason is that large body fat can shift the
distribution, provoking the settlement of L and Z y the adipose tissue and not in the blood and
the retina. And the third reason is that there are some enzymes that directly influence adiposity.
[26]
ROLES OF LUTEIN AND ZEAXANTHN IN AMD The Age-Related Eye Disease Study 2 (AREDS2), a clinical trial done in the US suggests that
L and Z intake may provide protection against the AMD. The original Age-Related Eye
Disease Study(AREDS1) declared that the daily supplementation with vitamins C and E, β-
carotene, zinc and copper at levels higher than the recommended reduced the risk of progression
to a more advanced AMD by about 25%.[27] In AREDS2, 10mg of Lutein and 2mg of
zeaxanthin were added to the supplementation [28] obtaining the next results:
L and Z supplementation lowered the progression of advanced AMD in people with low
dietary of L and Z.
In people with median intake of 696 µg of L and Z per 1000 calories per day, the
supplementation reduced the risk of having the AMD.
In people with median intake of 1134 µg of L and Z per 1000 calories per day, the
supplementation had no additional impact of progression of the disease when the
background was sufficient in L and Z.
This suggests that a median intake of 2268 µg of L and Z per 2000 calories per day may have a
protective effect against advanced AMD.
According to the Blue Mountains Eye Study(BMES) and Rotterdam Study(RT), L and
Z intake reduced more than 20% the risk of dry AMD in people with high genetic risk.
29
L and Z intake also affects the visual performance in people with AMD, causing
improvements in the visual acuity and contrast sensitivity in a dose-response manner.
Moreover, along with these progresses, the MPOD increases which means an
improvement of the fine-feature vision. It is thought that MPOD levels may impact
AMD. A 2016 meta-analysis of 20 randomized controlled trials found that L, Z and MZ
supplementation improves MPOD in healthy people and in people with AMD.
[29]
RECOMMENDED INTAKE VALUES FOR LUTEIN AND ZEAXANTHIN Although there are no official recommended dietary intake levels of L and Z, an intake of 5 to 6
mg per day is associated with lowering the risk of developing AMD and 12 mg per day with the
deceleration of AMD progression. However, it is not clear if these levels could have adverse
consequences over the decades and if they would differ in certain parts of the population.
Therefore, until these aspects remain unresolved, it is recommended to increase the
consumption of lutein-rich vegetables and fruits and moderately increase egg intake as well, for
healthy people. And for people with AMD, it is counselled to promote the daily intake of
antioxidants containing 12 mg of L and Z. [30]
Figure 39
30
CONCLUSION
To sum up it is clear that the eye is a complex organ whose correct functioning depends on the
collaboration of all its parts. In particular, the retina is a light sensitive layer that is responsible
for the image formation process and its central part, the macula, it essential for fine feature
vision. As a result, any alteration produced in this layer can have serious consequences such as
blindness like in the case of AMD, which is a really serious disease. The preventive measures
specified before need to be followed in order to reduce the risk of having this ocular disease. In
spite of the fact that there is no specific treatment for the dry AMD, the supplementation of L
and Z in the diet is beneficial for the eye, as they help its condition either by reducing the
progress of AMD in those who have it or by lessening the risk of having this disease up to 20%.
Moreover, L and Z have other positive effects such as they absorb blue light, protect us against
inflammation and improve our visual acuity and processing speed, the contrast sensitivity and
the photo stress.
Although, the values of intake of Lutein and Zeaxanthin are not determined, it is highly
recommended for healthy people and people with AMD to have a diet rich in green vegetables
and all type of food that contains L and Z as they are essential because as we have seen not only
enhance they the visual performance but also they have a protective effect in AMD.
As we can see the objectives of investigating about the anatomy of the eye, the AMD and the
macular pigments have been accomplished. Although it has not been possible to determine
specific values of L and Z, it is clear that these carotenoids are important for the eye health and
for the recovery of people with macular degeneration.
31
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