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Unit: IV
Minerals and trace elements and eye
Carotenoids and eye
Oxidative stress and the eye
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4.0 International (CC BY-NC-SA 4.0)
Unit: IV
Carotenoids and eye
Attribution-NonCommercial-ShareAlike
4.0 International (CC BY-NC-SA 4.0)
Carotenoids
• A class of fat soluble coloured pigments, found primarily in plants, where they play
a critical role in the photosynthetic process
• They are also found in non-photosynthetic microorganisms where they are known
to protect against the detrimental effect of excess light and oxygen
• derived from a 40-carbon polyene chain (C40H56)
• Changes in geometrical configuration about the double bonds located in the
backbone result in the formation of cis and trans isomers
• The hydrocarbon carotenoids are known as carotenes and include β-carotene, α-
carotene and lycopene.
• b-Carotene, the principal carotenoid found in carrots, is a major source of vitamin A
for the human body
Xanthophylls
• The xanthophylls are oxygenated derivatives of carotenes
• Two xanthophylls, lutein (L) and zeaxanthin (Z) accumulate at the macula where
they make up macular pigment (MP)
• In the human eye, the MP optical density (MPOD) is not uniformly distributed
across the retina
• It reaches its peak concentration in the central 1–2° of the fovea, and declines in an
exponential fashion to optically negligible levels by 5–10° radial eccentricity
• Structurally, L is an isomer of Z, which differs in the position of the double bond in
the 6-carbon ring located on the right side of the carbon chain
Xanthophylls
Property Lutein Zeaxanthin
Maximum absorption
spectrum
Below 500nm Above 500nm
Orientation in lipid bilayer
membrane
Two types of orientation:
perpendicular (similar to
zeaxanthin) or parallel to
membrane
Perpendicular to the
membrane
Scavenging action As effective as b-carotene
in quenching
singlet oxygen
As effective as b-carotene
in preventing auto-
oxidation of lipids
Xanthophylls
Xanthophylls
• The xanthophylls are oxygenated derivatives of carotenes
• Two xanthophylls, lutein (L) and zeaxanthin (Z) accumulate at the macula where
they make up macular pigment (MP)
• In the human eye, the MP optical density (MPOD) is not uniformly distributed
across the retina
• It reaches its peak concentration in the central 1–2° of the fovea, and declines in an
exponential fashion to optically negligible levels by 5–10° radial eccentricity
• Structurally, L is an isomer of Z, which differs in the position of the double bond in
the 6-carbon ring located on the right side of the carbon chain
• The predominance of Z in the macula may be explained by the fact that L can be
metabolized to Z
Spatial distribution of macular carotenoids
• The concentration in the most central part of the macula has been estimated to be
around 1 mmol/l
• an average mass of carotenoids per unit retinal area is 1.33 ng/mm2 the centre of
the fovea
• 0.81 ng/mm2 at 1.6– 2.5 mm eccentricity
• there is a decrease in the total mass of pigment per unit area from central to the
peripheral retina by a factor of almost 300
Sources
• Carotenoids are not synthesised de novo by animals
• carotenes cannot be converted to xanthophylls
• The highest amounts of L and Z, combined, are found in egg yolk
• maize and orange pepper have been shown to contain the highest amounts of L (60
mol%) and Z (37 mol%)
• Green leafy vegetables are good sources of xanthophylls, whereas yellow and
orange vegetables contain predominantly carotenes
Digestion, absorption and transport
• Naturally occurring carotenoids are found in the form of protein matrices called
carotenoproteins, which are the most important factor limiting carotenoid
absorption in the gastrointestinal tract
• Heating of food influences the availability of the carotenoids by denaturing the
carotenoproteins, thus improving its accessibility.
• excess heating reduces their availability by isomerization of all-trans double bonds
to cis configurations
• 60% of the xanthophylls, and 15% of the carotenes, present in foods are destroyed
during the cooking process
Digestion, absorption and transport
• Naturally occurring carotenoids are found in the form of protein matrices called
carotenoproteins, which are the most important factor limiting carotenoid
absorption in the gastrointestinal tract
• Heating of food influences the availability of the carotenoids by denaturing the
carotenoproteins, thus improving its accessibility.
• excess heating reduces their availability by isomerization of all-trans double bonds
to cis configurations
• 60% of the xanthophylls, and 15% of the carotenes, present in foods are destroyed
during the cooking process
Digestion, absorption and transport
• The carotenoids are exclusively transported in the non-polar core of lipoproteins,
with the distribution largely determined by the physical properties of the
carotenoids
• L and Z are found predominantly in high-density lipoproteins (HDL: 53%), with
lower proportions in LDL and very-lowdensity lipoproteins (VLDL) – 31% and 16%,
respectively
Factors affecting the bioavailability of carotenoids
Functions
• Vitamin A can be produced within the body from certain carotenoids, notably b-
carotene, a-carotene and cryptoxanthin
• Two main putative functions of the macular carotenoids, which are particularly
attractive in terms of maintaining macular health, include blue light filtration and
antioxidant activity.
Optical Filter
• The absorbance spectrum of MP peaks at 460 nm (blue light), thereby protecting
the macula from photo-oxidative damage
• The fundamental means of blue light-induced damage is the photodynamic
generation of free radicals
• It has been estimated that MP reduces the amount of blue light incident on the
fovea by approximately 40%.
• Light at 450 nm can damage retina than any other wavelength, it is at this
wavelength the MP absorbs maximum light
Optical Filter
• The filtering function of MP is particularly important in young individuals (30–40
years)
• This means that young individuals are at higher risk of macular exposure to blue
light, and this may represent a risk for AMD
• In addition, the absorption of short-wavelength blue light by MP reduces
chromatic aberration, as blue light has been primarily implicated in the image
degradation at the fovea
Antioxidant properties
• Kirschfeld apparently was the first to formulate the concept that carotenoids
protect the macula via their antioxidant property.
• Khachik and co-workers in 1997demonstrated the presence of direct oxidation
products of macular carotenoids in the human retina
• oxidative stress activates apoptosis. Carotenoids, by virtue of their antioxidant
activity, may protect against this phenomenon.
Singlet –Oxygen Quenching
• The carotenoids quench singlet oxygen primarily by a physical mechanism, in which
the excess energy of singlet oxygen is transferred to the electron-rich structure of
the carotenoid
• This added energy results in excitation of the carotenoid molecules into the triplet
state (3Car*)
• then the carotenoid relaxes to its ground state (1Car) by losing the extra energy as
heat.
• This activity is most significant to the retina
• Z containing 11 double bonds is a more effective quencher of singlet oxygen, when
compared with L.
Cataract
• Age-related cataract is the most common cause of visual impairment in elderly
people worldwide.
• Initially, the single-layered epithelium of the lens is damaged, followed by
aggregation and cross linkage of lens proteins, leading to cataract formation.
• It has been proposed that reactive oxygen species are generated through photo-
oxidation and metabolic processes in the lens, leading to the afore-mentioned
changes and thus contributing to the genesis of cataract.
Age-related macular degeneration
• AMD is the commonest cause of visual impairment in the western world, and
oxidative stressrepresents an increasingly plausible aetiological mechanism for this
condition.
• The retina is an ideal environment for generation of reactive oxygen
intermediates due to its high content of polyunsaturated fatty acids, its exposure to
high levels of visible light and oxygen, its wealth of chromophores and the continual
process of phagocytosis by the retinal pigment epithelium.
• The function of macular carotenoids remains uncertain; however, they may protect
against AMD through its filtering property, alone or in combination with its
antioxidant activity
Retinitis pigmentosa (RP)
• RP is a genetically and clinically heterogeneous group of incurable retinal
degenerative diseases.
• Aleman and co-investigators investigated MP in retinitis pigmentosa patients, and
observed no significant difference between patients and controls.
• In addition, when supplemented with L, augmentation of MP density is observed in
retinitis pigmentosa patients but is unaccompanied by an improvement in central
visual acuity.

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Carotenoids and eye

  • 1. Unit: IV Minerals and trace elements and eye Carotenoids and eye Oxidative stress and the eye Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
  • 2. Unit: IV Carotenoids and eye Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
  • 3. Carotenoids • A class of fat soluble coloured pigments, found primarily in plants, where they play a critical role in the photosynthetic process • They are also found in non-photosynthetic microorganisms where they are known to protect against the detrimental effect of excess light and oxygen • derived from a 40-carbon polyene chain (C40H56) • Changes in geometrical configuration about the double bonds located in the backbone result in the formation of cis and trans isomers • The hydrocarbon carotenoids are known as carotenes and include β-carotene, α- carotene and lycopene. • b-Carotene, the principal carotenoid found in carrots, is a major source of vitamin A for the human body
  • 4. Xanthophylls • The xanthophylls are oxygenated derivatives of carotenes • Two xanthophylls, lutein (L) and zeaxanthin (Z) accumulate at the macula where they make up macular pigment (MP) • In the human eye, the MP optical density (MPOD) is not uniformly distributed across the retina • It reaches its peak concentration in the central 1–2° of the fovea, and declines in an exponential fashion to optically negligible levels by 5–10° radial eccentricity • Structurally, L is an isomer of Z, which differs in the position of the double bond in the 6-carbon ring located on the right side of the carbon chain
  • 5. Xanthophylls Property Lutein Zeaxanthin Maximum absorption spectrum Below 500nm Above 500nm Orientation in lipid bilayer membrane Two types of orientation: perpendicular (similar to zeaxanthin) or parallel to membrane Perpendicular to the membrane Scavenging action As effective as b-carotene in quenching singlet oxygen As effective as b-carotene in preventing auto- oxidation of lipids
  • 7. Xanthophylls • The xanthophylls are oxygenated derivatives of carotenes • Two xanthophylls, lutein (L) and zeaxanthin (Z) accumulate at the macula where they make up macular pigment (MP) • In the human eye, the MP optical density (MPOD) is not uniformly distributed across the retina • It reaches its peak concentration in the central 1–2° of the fovea, and declines in an exponential fashion to optically negligible levels by 5–10° radial eccentricity • Structurally, L is an isomer of Z, which differs in the position of the double bond in the 6-carbon ring located on the right side of the carbon chain • The predominance of Z in the macula may be explained by the fact that L can be metabolized to Z
  • 8. Spatial distribution of macular carotenoids • The concentration in the most central part of the macula has been estimated to be around 1 mmol/l • an average mass of carotenoids per unit retinal area is 1.33 ng/mm2 the centre of the fovea • 0.81 ng/mm2 at 1.6– 2.5 mm eccentricity • there is a decrease in the total mass of pigment per unit area from central to the peripheral retina by a factor of almost 300
  • 9. Sources • Carotenoids are not synthesised de novo by animals • carotenes cannot be converted to xanthophylls • The highest amounts of L and Z, combined, are found in egg yolk • maize and orange pepper have been shown to contain the highest amounts of L (60 mol%) and Z (37 mol%) • Green leafy vegetables are good sources of xanthophylls, whereas yellow and orange vegetables contain predominantly carotenes
  • 10. Digestion, absorption and transport • Naturally occurring carotenoids are found in the form of protein matrices called carotenoproteins, which are the most important factor limiting carotenoid absorption in the gastrointestinal tract • Heating of food influences the availability of the carotenoids by denaturing the carotenoproteins, thus improving its accessibility. • excess heating reduces their availability by isomerization of all-trans double bonds to cis configurations • 60% of the xanthophylls, and 15% of the carotenes, present in foods are destroyed during the cooking process
  • 11. Digestion, absorption and transport • Naturally occurring carotenoids are found in the form of protein matrices called carotenoproteins, which are the most important factor limiting carotenoid absorption in the gastrointestinal tract • Heating of food influences the availability of the carotenoids by denaturing the carotenoproteins, thus improving its accessibility. • excess heating reduces their availability by isomerization of all-trans double bonds to cis configurations • 60% of the xanthophylls, and 15% of the carotenes, present in foods are destroyed during the cooking process
  • 12. Digestion, absorption and transport • The carotenoids are exclusively transported in the non-polar core of lipoproteins, with the distribution largely determined by the physical properties of the carotenoids • L and Z are found predominantly in high-density lipoproteins (HDL: 53%), with lower proportions in LDL and very-lowdensity lipoproteins (VLDL) – 31% and 16%, respectively
  • 13. Factors affecting the bioavailability of carotenoids
  • 14. Functions • Vitamin A can be produced within the body from certain carotenoids, notably b- carotene, a-carotene and cryptoxanthin • Two main putative functions of the macular carotenoids, which are particularly attractive in terms of maintaining macular health, include blue light filtration and antioxidant activity.
  • 15. Optical Filter • The absorbance spectrum of MP peaks at 460 nm (blue light), thereby protecting the macula from photo-oxidative damage • The fundamental means of blue light-induced damage is the photodynamic generation of free radicals • It has been estimated that MP reduces the amount of blue light incident on the fovea by approximately 40%. • Light at 450 nm can damage retina than any other wavelength, it is at this wavelength the MP absorbs maximum light
  • 16. Optical Filter • The filtering function of MP is particularly important in young individuals (30–40 years) • This means that young individuals are at higher risk of macular exposure to blue light, and this may represent a risk for AMD • In addition, the absorption of short-wavelength blue light by MP reduces chromatic aberration, as blue light has been primarily implicated in the image degradation at the fovea
  • 17. Antioxidant properties • Kirschfeld apparently was the first to formulate the concept that carotenoids protect the macula via their antioxidant property. • Khachik and co-workers in 1997demonstrated the presence of direct oxidation products of macular carotenoids in the human retina • oxidative stress activates apoptosis. Carotenoids, by virtue of their antioxidant activity, may protect against this phenomenon.
  • 18. Singlet –Oxygen Quenching • The carotenoids quench singlet oxygen primarily by a physical mechanism, in which the excess energy of singlet oxygen is transferred to the electron-rich structure of the carotenoid • This added energy results in excitation of the carotenoid molecules into the triplet state (3Car*) • then the carotenoid relaxes to its ground state (1Car) by losing the extra energy as heat. • This activity is most significant to the retina • Z containing 11 double bonds is a more effective quencher of singlet oxygen, when compared with L.
  • 19. Cataract • Age-related cataract is the most common cause of visual impairment in elderly people worldwide. • Initially, the single-layered epithelium of the lens is damaged, followed by aggregation and cross linkage of lens proteins, leading to cataract formation. • It has been proposed that reactive oxygen species are generated through photo- oxidation and metabolic processes in the lens, leading to the afore-mentioned changes and thus contributing to the genesis of cataract.
  • 20. Age-related macular degeneration • AMD is the commonest cause of visual impairment in the western world, and oxidative stressrepresents an increasingly plausible aetiological mechanism for this condition. • The retina is an ideal environment for generation of reactive oxygen intermediates due to its high content of polyunsaturated fatty acids, its exposure to high levels of visible light and oxygen, its wealth of chromophores and the continual process of phagocytosis by the retinal pigment epithelium. • The function of macular carotenoids remains uncertain; however, they may protect against AMD through its filtering property, alone or in combination with its antioxidant activity
  • 21. Retinitis pigmentosa (RP) • RP is a genetically and clinically heterogeneous group of incurable retinal degenerative diseases. • Aleman and co-investigators investigated MP in retinitis pigmentosa patients, and observed no significant difference between patients and controls. • In addition, when supplemented with L, augmentation of MP density is observed in retinitis pigmentosa patients but is unaccompanied by an improvement in central visual acuity.