ROle of selenium, Zinc in the eye, functions of zinc and selenium in the eye, Zn and the antioxidant mechanisms of eye General nutritional fact of calcium and its role in the body

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
Minerals and trace elements and eye
Attribution-NonCommercial-ShareAlike
4.0 International (CC BY-NC-SA 4.0)

3. Macro and Micro minerals
• It has been estimated that about 20 different minerals are required in the human
diet
• only seven have a well-established biological role
• Minerals are micronutrients because they are needed in very minute quantities,
and can be categorized into one of the two following groups based on the daily
requirement:
1) macrominerals
2) microminerals

4. Difference between macro and micro minerals
Macrominerals
• The daily requirement of
macrominerals exceeds 100 mg
• Calcium
• Phosphorus
• Potassium
• Sulfur
• Chloride
• Magnesium
Microminerals
• The daily requirement of
microminerals (trace elements) is
less than 100 mg
• Iron
• Zinc
• Copper
• Manganese
• Iodine
• Selenium

5. Macro and Micro minerals
• Mineral and trace element deficiency is more common than vitamin deficiency.
• Those at increased risk include elderly people because of reduced dietary intake
• A reduction in the stomach acid in the elderly further reduces the release of trace elements
from ingested foodstuffs, and hence decreases their absorption
• Deficient intake in association with reduced gastrointestinal absorption of minerals and trace
elements inevitably results in inadequate bioavailability of these compounds.
Increased age
Inadequate
bioavailability of
minerals
Reduced
dietary intake
Reduction in
stomach acid

6. Macro and Micro minerals
• With ageing, there is a general decline in the antioxidant defences of many organ
systems, including the eye
• The antioxidant system is dependent on a variety of nutritionally derived cofactors
• Oxidative stress has been proposed as the underlying mechanism for many age-
related eye diseases such as cataract and age-related macular degeneration (AMD)
• It is reasonable to hypothesise that a declining bioavailability of trace elements
could exacerbate the overall age-related reduction in antioxidant capability, and
contribute to the onset of various age-related eye diseases

7. Macro and Micro minerals
Antioxidant Enzyme Location Mineral
Superoxide dismutase Photoreceptors Zn, Cu, Fe, Mn
Glutathione peroxide Retina, RPE, lens Zn, Se, Cu, Fe
Catalase RPE, Lens Zn, Cu, Fe
Retinal reductase Retina Zn
Metallothionein RPE Zn

8. Zinc
(Zn2+ )
The essential trace
element or “helper
molecule”
Attribution-NonCommercial-ShareAlike
4.0 International (CC BY-NC-SA 4.0)

9. Zinc (Zn)
• Zn is the second most abundant trace element in the human body: total body
content is approximately 2 g
• It is an essential trace element, and is believed to play a role in maintaining the
health of the eye by protecting ocular tissues from agerelated wear and tear
• high concentrations of Zn in the retina–choroid complex: 463 mg/kg body weight of
the dried tissue
• Recent studies have shown that maximum concentration of Zn is present in
melanin-containing tissues of the eye, most notably the retinal pigment epithelium
(RPE)

10. Zinc (Zn)
• Other ocular tissues that contain Zn, in descending order of concentration, include:
(1) iris
(2) choroid
(3) sclera
(4) vitreous
(5) lens
(6) cornea
(7) retina

11. Zn and Vitamin A metabolism
• Zn plays an important role in the transport and metabolism of vitamin A
• In the retina, the conversion of retinol (circulating form) to retinal (active form) is
mediated by a Zn metalloenzyme - retinol reductase, an alcohol dehydrogenase
enzyme
Retinol
(Circulating form)
Retinal
(Active form)
Retinol
reductase
Zn2+
• Retinal is then utilised for the synthesis of rhodopsin
• Zn also affects the synthesis and/or release of retinol-binding protein in liver.

12. Antioxidant properties
• it stabilises the cellular membranes, thus protecting the cell against lipid
peroxidation
• This process is particularly important in retina, where high oxidative conditions
prevail
• loss of Zn from biological cell membranes, especially photoreceptors, increases
their susceptibility to oxidative damage and impairs their ability to function
properly.
First property

13. Antioxidant properties
• Zn induces the formation of metallothionein (MT), and combines with the thiol
group present on MT to form Zn–MT complexes
• When exposed to reactive oxygen intermediates (ROI), these complexes release Zn
molecules, which protect membranes and other cellular organelles against
oxidative damage
Second property
Thionein
(MT thiols)
Zn-MT
ROIZn
Thionin
(MT-disulfide)
Zn

14. Antioxidant properties
• Zn, with its high affinity for protein-sulfhydryl (SH) groups, may inhibit ROI from
interacting with these proteins at these SH sites
• The binding of Zn with protein-SH groups results in displacement of Fe2+ and
Cu2+ (ROI generators), which otherwise could interact with H2O2 in a Fenton-type
reaction with consequential generation of highly reactive hydroxyl molecules
Third property
2 Protein –SH
(contains Fe2+)
Protein –S-Zn-S-Protein
(misfolded protein)
Zn
Fe2+

15. Antioxidant properties
• Zn protects cells against oxidative damage indirectly through its action on several
enzymes involved in the generation of ROI
• (e.g. reduced nicotinamide adenine dinucleotide phosphate (NADPH)-oxidases)
• it also interacts with peptidases and hydrolases, which are crucial to the metabolism
of ingested ROI
• Zn also participates in the regulation of the antioxidant system through its effect on
catalase, the activity of which has been shown to decline in experimental animals
with Zn deficiency
• Zn stabilises the structure of antioxidant enzymes such as superoxide dismutase
(SOD)
Fourth property

16. Zinc and age-related macular degeneration
• An age-related decline of total Zn in human RPE, with the greatest decline in the
soluble fraction of macular RPE, and in eyes with signs of AMD.
• This decline, in turn, results in a reduction in MT and catalase antioxidant activity,
thus rendering RPE cells vulnerable to oxidative damage
• Age-Related Eye Disease Study (AREDS) showed that individuals at high risk for AMD
could slow the progression of advanced AMD by about 25 percent and visual acuity
loss by 19 percent by taking 40-80 mg/day of zinc, along with certain antioxidants.

17. Zinc and age-related macular degeneration
• Taking higher levels of zinc may interfere with copper absorption, which is why the
AREDS study also included a copper supplement.
• However, high doses of zinc may upset the stomach. Therefore, a follow-up study,
AREDS2, which is currently in progress, is testing a more moderate dose of 25
mg/day.

18. Zinc and cataract
• Zn is important in maintaining the health of the crystalline lens in the eye
• It is thought to reduce the risk for cataract formation by protecting the lens proteins
from oxidative damage.
• Zn deficiency has been associated with cataractogenesis in experimental animals.
• However, the results from various observational studies in humans show conflicting
results.

19. night blindness and RP
• Deficiency of Zn reduces the levels of plasma retinol-binding protein, and retinol
reductase, with resultant low levels of vitamin A in the retina
• Zn deficiency can result in alteration of dark adaptation and/or night blindness, and
that such changes can be reversed by supplementation of Zn.
Night Blindness
Retinitis Pigmentosa
• Zn inhibits photoreceptor apoptosis through scavenging of intracellular ROI,
establishing oxidative stress as a possible mediator of photoreceptor apoptosis in RP

20. Zinc and optic nerve diseases
• A deficiency of Zn may play a role in the pathogenesis of certain toxic and
nutritional optic neuropathies
• Zn stabilizes microtubules, which are necessary for axonal transport in neural tissue
this leads to neural diseases that involves optic nerves
• An autosomal disease in Zn absorption (acrodermatitis enteropathica) axonal
transport of nerve tissue is damaged
• This manifest as optic nerve disease which include optic nerve atrophy
• Similar manifestations are seen in TB medications using ethambutol which induces
causes Zn deficiency

21. Zinc and cornea
• Zn may play a role in the corneal repair process
• studies indicate that epithelial and stromal corneal wound-healing is markedly
delayed in Zn deficient animals

22. Daily intake
• 11 mg/day of zinc for men and 8 mg/day for women.
• For those at high risk for AMD, the AREDS study showed that higher levels of zinc
(40-80 mg/day) is beneficial.
• Zinc supplementation has been known to interfere with copper absorption, so it is
strongly recommended that people taking zinc also take 2 mg/day of copper.

23. Food sources with Zinc
• red meat, seafood, poultry,
eggs, wheat germ, mixed
nuts, black-eyed peas, tofu
and beans.

24. Selenium
(Se )
The metal element in
the antioxidant
enzyme GSH
Attribution-NonCommercial-ShareAlike
4.0 International (CC BY-NC-SA 4.0)

25. Selenium (Se)
• Se is an essential trace element with important antioxidant properties, and is the
metal element in the antioxidant enzyme GSH
• GSH is an Se-dependent enzyme, consisting of four identical subunits with an atom
of Se
• Present as seleno-cysteine, at each active site
• This natural sulphur-bearing peptide, found in the cytosole and mitochondria, acts
in conjunction with vitamin E to protect cells against free radical damage by
preventing lipid peroxidation

26. Selenium (Se)
NADPH + H+
NADP+
GSSH
Lipid
peroxide
Tissue
damage
2GSH
GSH
peroxide
GSH
reductase
B-oxidation
Hydroxy acids
Vitamin E
Polyunsaturated
fatty acids
Membrane
disintegration
(Se)

27. Selenium (Se)
• The most concentrated food source
for Se is the Brazil nut: a single nut
contains 120 μg of Se.
• Other natural sources include
seafood, meats, cereals (oat and
brown rice), dairy products, fruit and
vegetables (in descending order of
importance).
Sources

28. Selenium (Se)
• The concentration of Se in food sources depends on the level of Se in the soil in
which the plant has been grown, as the distribution of Se on the Earth’s crust is
uneven.
• Due to decreased soil content of Se, there is widespread deficiency in many parts
of China, the USA and Finland.
• declining levels of Se in the soil - due to acid rain and heavy use of chemical
fertilisers.
• fertiliser is often fortified with Se in order to augment Se intake of the population.
• The reference nutrient intake of Se is 60–75 μg/day
• Se is possibly harmful if taken in excess.
Sources

29. Selenium (Se)
• Selenium is LIKELY SAFE for most people
when taken by mouth in doses less than
400 mcg daily, short-term.
• Selenium is POSSIBLY UNSAFE when
taken by mouth in high doses or for long-
term - selenium toxicity.
• increase the risk of developing diabetes.
• High doses - nausea, vomiting, nail
changes, loss of energy, and irritability.
• Poisoning from long-term use - hair loss,
white horizontal streaking on
fingernails, nail inflammation, fatigue,
irritability, nausea, vomiting, garlic
breath odor, and a metallic taste
• muscle tenderness, tremor, light
headedness, facial flushing, blood
clotting problems, liver and kidney
problems, and other side effects.
Side effects

30. Selenium and cataract
• There is a very high concentration of GSH in the lens, where it acts as an
antioxidant and is a key protective factor against intra- and extralenticular toxins
• A lack of Se to activate GSH impedes the destruction of peroxides/free radicals in
the lens, leading to accumulation of free radicals, and consequential cataract
formation
• GSH is found to be low in all cases of cataract, and the activity of GSH in lens is
significantly reduced in Se-deficient animals

31. Selenium and age-related macular degeneration
• evidence is accumulating that oxidative damage may play an important role for
AMD
• GSH forms part of the complex antioxidant system of photoreceptors and RPE that
protects the retina from oxidative damage.
• There is a strong positive correlation between the dietary intake of Se and tissue
GSH activity
• In laboratory animals, experimental Se deficiency is associated with increased
lipid peroxidation
• This finding is consistent with the view that the age-related decline in plasma Se
levels would result in increased retinal oxidative injury and thereby contribute to
the development of AMD.

32. Other trace elements
• Mn functions primarily as a component of the antioxidant enzyme superoxide
dismutase (SOD), which limits the damaging effects of the superoxide free radical
from destroying cellular components
• Mn, therefore, may prevent cataract formation via its antioxidant properties, as
development of age-related cataract is ultimately related to oxidative damage.
• Studies have observed that SOD has a protective effect in the antioxidant defence
of cultured lens epithelial cells.
Manganese

33. Calcium
(Ca2+ )
The most
abundant
mineral in the body
Attribution-NonCommercial-ShareAlike
4.0 International (CC BY-NC-SA 4.0)

34. Calcium
• Calcium (Ca) is the most abundant mineral in the body
• body needs adequate dietary calcium (alongside vitamin D and several other
nutrients such as vitamin K) to develop and maintain healthy bones and teeth.
• Ca2+ also plays a vital – as a secondary messenger in intracellular signalling, the
transmission of information via the nervous system, the control of muscle
contraction (including the heart) and blood clotting.
• it has been suggested that adequate calcium intake (for example from reduced fat
dairy products) may help lower high blood pressure and may help protect against
colon cancer

35. Calcium
• The skeleton contains about 99% of the body’s calcium with approximately 1kg
present in adult bones
• Total calcium in the human body is about 1 to 1.5 kg, 99% of which is seen in bone
and 1% in extracellular fluid.
• The major constituents of bone are calcium and phosphate, forming
hydroxyapatite, which is associated within a meshwork of collagen fibres to form a
rigid structure
• The body’s requirement for calcium fluctuates with the rate of bone development,
the skeleton acts as a ‘bank’ of minerals from which calcium and phosphorus may
be continually withdrawn or deposited to support physiological requirement.

36. Calcium
• The skeleton contains about 99% of the body’s calcium with approximately 1kg
present in adult bones
• The major constituents of bone are calcium and phosphate, forming
hydroxyapatite, which is associated within a meshwork of collagen fibres to form a
rigid structure
• The body’s requirement for calcium fluctuates with the rate of bone development,
the skeleton acts as a ‘bank’ of minerals from which calcium and phosphorus may
be continually withdrawn or deposited to support physiological requirement.

37. Calcium
• Milk is a good source for calcium.
• Calcium content of cow’s milk is about 100 mg/100 mL
• Egg, fish and vegetables are medium sources for calcium
• Cereals (wheat, rice) contain only small amount of calcium. But cereals are the
staple diet in India. Therefore, cereals form the major source of calcium in Indian
diet.
Sources

38. Calcium
• An adult needs 500 mg per day and a child about 1200 mg/day
• Requirement may be increased to 1500 mg/day during pregnancy and lactation
• After the age of 50, there is a general tendency for osteoporosis, which may be
prevented by increased calcium (1500 mg/day) plus vitamin D (20 mg/day).
Daily Requirements of Calcium

39. Increased Absorption
• Vitamin D induces the synthesis of the
carrier protein (Calbindin) in the
intestinal epithelial cells
• parathyroid hormone: It increases
calcium transport from the intestinal
cells by enhancing 1α hydroxylase
activity.
• Acidity favors calcium absorption.
• Lysine and arginine increase calcium
absorption.
Decreased Absorption
• Phytic acid: Hexaphosphate of inositol is
present in cereals.
• Oxalates: present in some leafy
vegetables, which cause formation of
insoluble calcium oxalates.
• Malabsorption syndromes: Fatty acid is
not absorbed, causing formation of
insoluble calcium salt of fatty acid.
• Phosphate: High phosphate content will
cause precipitation as calcium
phosphate. The optimum ratio of
calcium to phosphorus is 1:2 to 2:1 as
present in milk.
Calcium

40. Calcium
• The term denotes that the blood calcium level is more than 11 mg/dL.
• The major cause is hyperparathyroidism. This may be due to a parathyroid adenoma
or an ectopic PTH secreting tumor
• osteoporosis and X-ray shows punched out areas of bone resorption. Pathological
fracture of bone may result
• In the blood, calcium and alkaline phosphatase levels are increased, while
phosphate level is lowered.
• iv. In urine, calcium is excreted, which may cause inhibition of elimination of
chloride. This may lead to hyperchloremic acidosis. Calcium may be precipitated in
urine, leading to recurrent bilateral urinary calculi.
• Ectopic calcification may be seen in renal tissue, pancreas (pancreatitis), arterial
walls, and muscle tissues
Hypercalcemia

41. Calcium
• Hyperparathyroidism
• Multiple myeloma
• Paget’s disease
• Metastatic carcinoma of bone
• Thyrotoxicosis, Addison’s disease
• Benign familial hypercalcemia
• Dehydration
• Prolonged immobilization
• Tuberculosis, leprosy, sarcoidosis
• Milk-alkali syndrome
• Drugs like Thiazide diuretics, Excess
vitamin D or vitamin A, Excess calcium
given IV
Causes of Hypercalcemia

42. Symptoms
• Anorexia, nausea, vomiting
• Polyuria and polydypsia (ADH
antagonism)
• Confusion, depression, psychosis
• Renal stones
• Ectopic calcification and pancreatitis
• Blood alkaline phosphatase is
increased.
Management
• Adequate hydration, IV normal saline
• Furosemide IV to promote calcium
excretion
• Steroids, if there is calcitriol excess
• Beta blockers in thyrotoxicosis
• Definitive treatment for the underlying
disorder.
Calcium
Hypercalcemia

43. Calcium
• If serum calcium level is less than 8.5 mg/dL, there will be mild tremors. If it is lower
than 7.5 mg/dL, tetany, a life-threatening condition will result
• Tetany may be due to accidental surgical removal of parathyroid glands or by
autoimmune diseases.
• In tetany, neuromuscular irritability is increased.
• Main manifestation is carpopedal spasm - Laryngeal spasm may lead to death.
• Chvostek’s sign (tapping over facial nerve causes facial contraction) will be positive
• Trousseau’s sign (inflation of BP cuff for 3 minutes causes carpopedal spasm) could
be elicted
Hypocalcemia

44. Calcium
• Deficiency of Vitamin D
Decreased exposure to sunlight,
Malabsorption, dietary deficiency, Hepatic
diseases, Decreased renal synthesis of
calcitriol, Nephrotic syndrome
• Deficiency of Parathyroid
• Increased Calcitonin
Medullary carcinoma of thyroid, Ectopic
secretion of tumors
• Deficiency of Calcium
Intestinal malabsorption, Acute
pancreatitis, Infusion of agents complexing
calcium, Alkalosis decreasing ionized
calcium
• Deficiency of Magnesium
• Increase in Phosphorus level
Renal failure, Phosphate infusion, Renal
tubular acidosis
• Hypoalbuminemia
Causes of Hypocalcemia

45. Symptoms
• Muscle cramps
• Paresthesia, especially in fingers
• Neuromuscular irritability, muscle
twitchings
• Tetany (Chvostek’s sign, Trousseau’s
sign)
• Seizures
• Bradycardia
• Prolonged QT interval
Management
• Oral calcium, with vitamin D
supplementation
• Underlying cause should be treated
• Tetany needs IV calcium - usually 10 mL
10% calcium gluconate over 10 minutes,
followed by slow IV infusion.
• IV calcium should be given only very
slowly.
Calcium
Hypocalcemia
Carpopedal spasm in tetany

46. Calcium
• After the age of 40–45, calcium absorption is reduced and calcium excretion is
increased; so, there is a net negative balance for calcium.
• After the age of 60, osteoporosis is seen. Then there is reduced bone strength and
an increased risk of fractures
• Decreased absorption of vitamin D and reduced levels of androgens/estrogens in old
age are the causative factors
• Interleukin-1 and 6 also play important roles in the genesis of the condition
• Osteoporosis is more severe and starts early in Indians, compared to Westerners.
• Treatment in the advanced phase of osteoporosis (OP) is not sufficient to prevent
bone fracture. So, early diagnosis of OP is done by bone mineral density (BMD).
Osteoporosis