structure of lens and changes during cataractogenesis
TRANSCRIPT
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Structure of lens
and
changes during cataractogenesis
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Structure of Human Eye
1. Outer fibrous layer.
Sclera: Tough, fibrous, opaque coat.
Cornea: Clear, transparent, avascualar.
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Wall of the eye ball contain 3 principle layers:
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2. Middle Vascular
layer.
Choroid: bluish vascular
structure ( uveal layer).
Ciliary body: continuation of
choroid anteriorly, contains
ciliary muscle.
Iris: pigmented, opaque
muscular structure
containing sphincter pupillae
and dilator pupillae.
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Structure of Human Eye continued…
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Structure of Human Eye continued…
3. Inner nervous
layer:
Retina: Outer
epithelial cells,
inner nerve cells.
Other
structures:
Aqueous humour:
Vitreous humour:
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Structure of human lens
The lens is a transparent, encapsulated,
biconvex body lies between iris and the
vitreous body with no blood supply.
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Definition
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AP
Structure of lens under compound microscope
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capsule
epithelium
Cortex Lens fiber cells
Nuclear lens fiber cells
PP
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Development of Human lens
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Development of Human lens continued…
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Structure of mature lens
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Anterior pole
Posterior poleaxis
equator
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Gross structure of lens
Dimensions:
◦ Equatorial diameters
birth: 6.5mm
15 years of age: 9.0mm
90 years of age: 9.5mm
◦ Axial dimensions:
birth: 3.5 – 4.0mm
95 years of age: 4.75 – 5.0mm
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Gross structure of lens continued...
◦ Radii of curvature:
reduce through out life.
Anterior surface: 10mm
Posterior surface: 6mm
◦ Refractive power:
Unaccomodated state: 20 diopters
Maximum accommodation state: 14 diopters ( 8 – 12
years of age)
Accommodation decreases with age approaching
ZERO after 50 years.
Weight: Adult lens is 1g.
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The lens capsule
Capsule is a transparent basement
membrane completely surrounding the lens.
◦ thickness: in 35 years old lens.
at posterior pole: 4µm
at anterior pole: 21µm
Synthesis:
anterior capsule: epithelial cells.
posterior capsule: elongating fiber cells.
Major components: collagen type 4, laminin,
entactin, heparan sulphate, proteoglycan and
fibronectin.12
capsule
Epithelial cells
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The lens capsule continued…
Zonular fibers insert into capsule near the
equator region called ZONULAR
LAMELLA.
Functions of capsule:
1. During accommodation.
2. Barrier function.
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The lens epithelium
Shape and size:
Polygonal cuboidal.
Height: 5-8µm
Width: 13µm.
Epithelial cell density:
Men: 3900 cells/mm sq
Woman: 5780cells/mm sq
All organelle are present and lateral membranes
are connected by desmsomes and gap junctions.
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The lens epithelium continued…
Cytoskeletal elements: actin, myosin,
vimentin, microtubules, spectrin and alfa actinin.
Only a band of cell in the equatorial region
remains mitotically active throughout life called
as germinal zone.
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Shape:
◦ Young state: flattened,
hexagonal cross sectional
profile.
◦ Middle age: irregular
profile.
Dimensions:
◦ Length: 7-10mm
◦ Width: 10-12µm
◦ Thickness: 1.5 - 2µm
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The lens fibers
Corticle fibers lack nucleus and all cell organelles.
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The lens fibers continued…
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Note alternating rows of hooks and
complementary eyes. Spines hook
into next row of eyes to interlock
layers like Velcro.
Note ball and socket joint
interlocking at superficial cortical
fiber edges. Planar surface of
fibers interlock with next layer of
offset fibers (removed).
Lateral membranes have interdigitations like ball and
socket, tongue and groove (hook and eye) junctions
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The lens fibers continued…
The lens fiber cells are joined by desmosomes and
gap junctions.
Crystallin proteins:
90% of the total mass of the fiber.
40% of the wet weight of the lens fiber.
Crystallin concentration:
In cortex: 15%
In nucleus: 70%
responsible for gradient refractive index.
The border between the apical membrane of the anterior
epithelium and the apical membrane of the elongating fiber
is known as Epithelium Fiber Interphase.
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The lens sutures
Appears during 8 – 9
months of fetal life.
Only secondary lens
fibers are responsible.
Symmetrical Y pattern in
the anterior section and a
symmetrical inverted Y
pattern at the posterior
section appears.
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One lens fiber attached to the limb
of the Y near the anterior pole is
attached to the fork of opposite Y
near the posterior pole and vice
versa.
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The lens sutures continued…
Branches of the suture:
o In early adulthood : 6-9
o In middle to old age: 9-15
Finally a star shaped suture is formed at both the poles.
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Lens crystallin proteins
40% of wet weight of lens fiber.
High concentration of crystallin (400mg/ml)
than that of a typical cell.
Crystallin proteins classification:
1. Classical.
2. Taxon spesific.
• Adult human lens do not produce taxon
specific crystallins.
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Lens crystallin proteins continued…
α- crystallins are the members of small heat
shock proteins having chaperone activity.
α- crystallins are also enzymes- serine
threonine autokinase activity.
α- crystallins are flexible and the complexes
are plastic.
β- crystallins have a tendency to form
multimers but γ- crystallins exist as
monomers.
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Lens crystallin proteins continued…
Six β- crystallin polypeptides: βA1, βA3, βA4, βB1, βB2, βB3
Three γ- crystallins: γS, γC, γD
For the electrophoretic study lens protein components are separated as:
1. Water soluble fraction.
2. Urea soluble fraction.
3. Detergent soluble fraction.
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Structural properties maintaining
transparency of the lens.
1. Organization of the lens fiber in the lens.
2. The refractive power of the lens is altered as
the lens grows, maintaining focal point
constant.
3. Variable concentration of crystallin proteins
causes gradient of refractive index partially
corrects for spherical aberration.
4. All the cell organelles are absent in cortical
and nuclear fibers.
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1. ATP dependent bicarbonate pump activity:
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Metabolic reactions maintaining
transparency of the lens
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Metabolic reactions maintaining transparency of the lens continued…
2. Glucose metabolism in lens:
glycolysis: 85%
hexose monophosphate pathway: 10%
Citric acid cycle: 3% presumably by the cells
located at the periphery.
3. Low oxygen tension (15mmHg or 2%of O2)
protect the lens from oxidative damage.
4. Ascorbic acid concentration is 20 times in
the aqueous humour than the blood (Blood
level: 23-85µM).
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Metabolic reactions maintaining transparency of the lens continued…
5. Reduced glutathione is present in high
concentration in aqueous humour: 4-6mM.
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Metabolic reactions maintaining transparency of the lens continued…
6. High concentration of transferrin in
epithelial cells, catalase and glutathione
peroxidase prevent oxidative stress.
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Fe+2
transferrin
catalase
Glutathione
peroxidase
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Cataract
Definition: Cataract is defined as any opacity
the lens causing scattering of the light
transmitted.
Major classification of cataract:
1.Etiological classification
2.Morphological classification
3.Maturity of the cataract
4.Age onset
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Etiological classification
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Etiological classification continued…
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Classification of cataract according to maturity
1. Immature
2. Mature
3. Intumescent
4. Hypermature
5. Morganian
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Classification of cataract according to age onset
1. Congenital
2. Juvenile
3. Senile
4. Infantile
5. Presenile
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Cataractogenesis
General mechanism of cataract formation
1. Opacification of previously clear lens fiber.
2. Formation of new opaque fibers.
3. Deposition of the granular material instead
of fibers.
4. Accumulation of pigments.
5. Opacification of the lens epithelium.
6. Deposition of extraneous material.
7. General mechanism involve oxidation,
osmotic effect, phase separation, chemical
modification of proteins.34
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Age related changes during cataractogenesis
Morphologic changes: Capsule thickens,
appearance of organelle changes, epithelial cell
density decreases, loss of polygonal cross
sectional profile, vacuoles and multilamellar
bodies observed, plasma membrane disrupted.
Biophysical changes: Optical quality
decreased, increase in the absorbance near blue
region - tritanopia like defects observed in older
people, accommodation loss and reaches to zero
by the age 50 years.
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Age related changes during cataractogenesis continued…
Physiologic changes:
◦ Membrane potential decreases,
at 20 years: -50mV
at 60 years: -30mV
Na+ and Ca2+ concentration increases after the
age 40.
Relative lens permeability increases.
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Biochemical changes in the lens with aging
In general:
◦ metabolic activities decline.
◦ Proteins undergo post translational, covalent,
conformational modifications
◦ Enzymes loose activity and become more heat
labile.
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Biochemical changes in the lens with aging continued…
SDS-PAGE protein profile confirms chemical modification
and partial degradation, cleavage product of native protein.
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Biochemical changes in the lens with aging continued…
α- crystallin concentration decrease whereas
γS, β- crystallins increase.
At the age of 42 years approximately 50%
of α, β and γ-crystallins become water
insoluble.
Major plasma membrane protein MIP-26
undergo radical modification.
Racemization of Asp, Met, Tyr and
deamidation of Gln, Asn of the crystallin
proteins occur.
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Biochemical changes in the lens with aging continued…
Cytoskeletal proteins like vimentin,
intermediate filaments are disassembled
because of insolubalisation and proteolysis.
Increased non-enzymatic glycation of
crystallin proteins increase high molecualr
aggregates, scattering the light.
Intercellular transport decreases can not
have control over oxidative stress.
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Changes during cataractogenesis in diabetes
Human lens is affected only in severe
diabetes.
Two important recations responsible:
1. Non-enzymatic glycation of crystallin proteins.
2. Increased activity of aldose reductase.
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Non-enzymatic glycation of crystallin proteins
Difference between glycosilation and
glycation.
Glycation reaction principle.
Non-enzymatic glycation of crystallin
proteins occurs at amino group of Lys
reciduces.
In diabetes the process occurs twice as often
as in normal individual of comparable age.
Crystallin proteins become insoluble and
make high molecular weight aggregates.42
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Step: 1. Ca+2 promotes the binding of protein of RMM 43KD to the
plasma membrane.
Step: 2. Crystallin becomes bound to the protein by disulphide bridges
forming light scattering aggregates.
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Increased activity of aldose reductase
Km of aldose reductase for glucose is
about 200mM.(Normal concentration of
blood glucose is 4-6.1mM/L)
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Aldose reductase
D-fructose
Aldehyde
dehydrogenase
D-glucose D-sorbitol
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Changes during cataractogenesis in
galactosemia
Galactokinase or galactose-1-phosphate
uridyl transferase deficiency.
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Changes during cataractogenesis
caused by ionising radiation
X- rays affect germinative zone of the
epithelial layer.
Organisation of the fiber cell is disrupted.
Membrane permiability increases. Synthesis
of protein, potassium, glutathione
concentration decline. Sodium concentration
increases.
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Changes during cataractogenesis
caused by non ionising radiation
High lifetime exposure to UV light causes
cortical cataract.
UV-B reaching the eye is mainly responsible
than UV-A reagion.
Mechanism is by free radical damage.
Long term exposure to infra red and high
energy microwaves can cause cataract
characteristically referred as “Glass
Blowers” cataract.
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Normal Vs Cataractous Lens
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Non surgical management of cataract
1. Proper correction with the glasses,
mydriatic agents, use of dark glasses.
2. Medical treatment to delay progression of
cataract:
i. Aldose reductase inhibitor: oral aspirin 50-
100mg/kg, quercetin 200-400mg/kg, topical
sorbinil and sulidac drops.
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Non surgical management of cataract continued…
ii. Antioxidants: β-carotene, α-tocopherol,
ascorbic acid.
iii. Membrane stabilising agents: Benzadec and
Benzyl alcohol(0.07%)
iv. Miscellaneous: Iodides of calcium,
potassium, homiopathic drugs like cinireria,
maritima.
Unfortunately none of the drug have been
conclusively proven to be anticataractogenic.
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References:
1. Grays Anatomy
2. Wills biochemical basis of medicine.
3. Text book of biochemistry with clinical
correlation. – Thomas. Devlin.
4. Text book of biochemistry. – Bhagwan.
5. The text book of opthomalogy, volume 3, Lens &
Cataract. - Norman. S. Jaffe, Joseph. Horwitz.
6. Adler’s physiology of the eye: Clinical
applications.-Paul. L. Kaufman, Albert ALM.
7. Essentials of opthomalogy- Sanar. K. Basak.
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Thank You 54
Thank You
Thank You
Thank You