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LENS – ANATOMY AND PHYSIOLOGY

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EMBRYOLOGY

EYEBALL DEVELOPMENT• - Outgrowth from prosencephalon

called optic vesicle• - Specialised area of surface ectoderm

called lens placode

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• Lens placode is identified by 27 days gestation• Lens placode invaginates sinus below

surface ectoderm to form lens vesicle- Lens vesicle – single layer of cells

covered by a basal lamina

- Primary lens fibres –

develop from posterior wall of vesicle- Secondary lens fibres –

develop from equatorial cells of ant.epithelium

- Tunica vasculosa lentis – surrounds lens by

9 weeks

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EMBRYONIC NUCLEUS – 1 – 3 Months of GA

- Sutural pattern - 2 Y sutures

FETAL NUCLEUS – 3 months GA – Birth

INFANTILE NUCLEUS – Birth to puberty

ADULT NUCLEUS - Adults

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• Lens – Trasparent , Biconvex , crystalline structure

Location – PATELLAR FOSSA – saucer shaped depression

Posterior capsule of the lens is attached to the vitreous with

WEIGERT ‘S LIGAMENT – A circular area of attachment

between the hyaloid face and the lens

capsule – potential space called the BERGER ‘S SPACE

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DIMENSIONS

Equatorial diameter of lens – 6.5mm at birth ,increases to 9-10 mm in second decade

Thickness – 3.5 mm at birth ,increases to 5 mm with increase in age

Weight – 255 mg at 40 – 50 years of age

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• SURFACES• - Anterior surface – Part of a sphere of radius 10 mm(8-14)

Centre – Anterior pole• - Posterior surface – More curved than anterior -6 mm

Centre – Posterior pole• - The two surfaces meet at the equator

- REFRACTIVE INDEX

Nucleus – 1.42

Cortex – 1.38

Refractive power – 16-17 dioptres

Accomodative power – 14-16 D at birth

- 7 – 8 D at 25 years of age

- 1 – 2 D at 50 years of age

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• BIOMICROSCOPIC STRATIFICATION OF LENS

- Capsule

- Superficial cortex – 3 zones – C1α,C1β,C2

- Deep Cortex – C3 and C4

- Nucleus

SURGICAL ANATOMY

- Capsule

- Cortex

- Epinuclear plate

- Nucleus

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STRUCTURE OF THE LENS

• LENS CAPSULE - Thickest BM in the body – 2- 20um thick

- Type 4 Collagen and GAG

-Thinnest at posterior pole

- Ultramicroscopy – Lamellar appearance – lamellae fine filaments

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-Lens capsule is similar to other basement membranes in

the body – Glomeruli , Blood vessels, spleen ,lung

-Pseudo exfoliation of lens capsule – abnormal formation of capsule like material on the lens capsule,ciliary processes,posterior iris layer

- True exfoliation – Lamellar splitting of the capsule – found among glassblowers

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ANTERIOR LENS EPITHELIUM

- 3 Zones

-Central zone – Cuboidal cells with round apically located nuclei

- Normally no mitosis occurs here

- Metaplasia – Myofibroblasts – Shield cataract

and glaucomflecken

-Intermediate zone – Smaller and more cylindrical cells –Mitosis+

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-Germinative zone – Columnar peripheral cells – pre equatorial

- Actively divide to form new cells

- New cells migrate posteriorly – Lens fibres

- Dysplasia –PSCC – radiation etc

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• Lens epithelium is Metabolically very active• Has a prominent cytoskeletal framework• Lateral membranes of the cells – have gap junctions-

Contains Na- K ATPases and Acid phosphatases• Apical membrane of Lens epithelium ---- interfaces ---

apical membrane of fiber cells – Epithelial Fiber cell interface

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• LENS FIBRES

- Derived from anterior epithelium –hexagonal in cross section

- Newer fibres are laid upon older ones – high ribosomal content

- New fibres have nuclei temporarily and later disappears

- LENS BOW or NUCLEAR BOW

- The areas in which anterior and posterior fibres meet are called the

sutures – there are 2 Y shaped sutures in early stages of

human lenses

- Later on – irregular dendritic pattern forms.

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• CILIARY ZONULES• Zonules of Zinn or suspensory ligaments of lens

• They run from ciliary body and fuse into lens capsule at equator

• Fibres are made up of glycoproteins and mucopolysaccharides• Microfibrils have a diameter of 8-40nm

• 3 types of zonular fibres

- First type fibres – THICK STRONG fibres

- Second type fibres – THIN FLAT

- Third type fibres – Very fine and run a circular course

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• OLD CONCEPT OF ARRANGEMENT• Orbiculo- posterior capsular fibres – second type• Orbiculo – anterior capsular fibres – first type• Cilio –posterior capsular fibres – arise from the valleys• Cilio – equatorial fibres – third type fibres – abundant in

young people – decrease with age

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• NEW CONCEPT OF ARRANGEMENT • Pars orbicularis –arise from posterior end of pars plana upto 1.5 mm

from the ora serrata• Zonular fibres – lie in the valley between ciliary processes• Zonular fork• Zonular limbs - Anterior limb – dense and insert at 1.5 mm from equator

- Equatorial limb

- Posterior limb

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CANAL OF HANNOVER – Circumferential space between anterior and posterior zonular fibres around the equator of lens

• Zonules have 7% cysteine and failure to convert the amino acid homocysteine into cysteine results in broken zonules and dislocated lenses in homocystinuria

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• LENS – Composed of water (65%) and proteins(34%)• Other constituents are Lipids ,Inorganic Ions ,Glucose(1%)

• WATER

- Lens is a relatively dehydrated organ

- Dehydration is maintained by the Active sodium pump

- Cortex is more hydrated

- No significant alteration in lens water with age

BIOCHEMICAL COMPOSITION

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• LENS PROTEINS

• Lens proteins

SolubleCrystallins (85%)

InsolubleAlbuminoids(15%)

Alpha crystallins

Beta crystallins

Gamma crystallins

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• Protein content of lens is higher than that of any organ in the body

• Other minor proteins in the lens are Phosphoproteins, Glycoproteins, Lipoproteins ,Flourescent proteins

• As lens ages , Soluble alpha crystallins get gradually converted to albuminoids

• Cortex – rich in Crystallins• Nucleus – rich in Albuminoid• Lens proteins – Immunologically privileged site

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• Amino acids in the lens – All amino acids except Tryptophan , Cysteine and hydroxyproline

• Higher concentration of amino acids in lens compared to

Aqueous humor and vitreous humor

• Amino acids are actively transported into the lens - ensures that the protein synthesis is not hampered

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• Amino acid concentration of lens is not affected by Ageing, fasting or starvation

• Glutathione is a chief constituent – it exists in the reduced

state (GSH) in the lens .Acts as an anti-oxidant in the lens

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• CARBOHYDRATES

- Lens contains glucose, fructose and glycogen

- Glucose level of normal lens is 20-120mg%

- Source – aqueous humor

- Glucose in lens is 1/10th of aqueous

- Glycogen in mainly in the nucleus and replaces gamma

crystallins with age

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- Sorbitol , Inositol , Gluconic acid ,Glucosamine are also

found- Ascorbic acid – high concentrations in the lens -

involved in oxidation – reduction systems in the lens

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• LIPIDS

- Lipids represent 2% of the dry weight of lens

- Lipids – Cholesterol(50%)

- Phospholipids(45%) - mainly sphingomyelin

- Glycosphingolipids and ceramides(5%)

- They constitute major part of lens fibre membranes

- Decrease in their synthesis or impaired degradation ----

membrane damage and lens opacities

- Sphinomyelin and its precursor – ceramides – increase in

senile cataracts.

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METABOLIC PATHWAYS

GLUCOSE METABOLISM • Occurs via 4 pathways • GLYCOLYSIS • KREB S CYCLE• HMP SHUNT PATHWAY• SORBITOL PATHWAY

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PATHWAY INTERMEDIATES END PRODUCTS GLUCOSEMETABOLISED(%)

NO.OFATP

Glycolysis Glu-6-po4 , fru-1,6-dipo4, pyruvate

Lactate 80% 2

Kreb’s cycle Tricarboxylic acids CO2,H20, 5% 36

HMP shunt Pentoses Co2,NADPH 15% -

Sorbitolpathway

Sorbitol, Fructose

Lactate 2

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• WATER AND ELECTROLYTE TRANSPORT

-Electrolyte and water content of lens resembles an intact

cell while that in the aqueous n vitreous resembles plasma

-Na+-K+ ATPase in the anterior epithelium uses ATP to extrude Na + and take up K+ into the cell by Active transport

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- Cations – Na , K – 145 mEq/L and Anions – 50-60mEq/L. - The equilibrium is disrupted if concentration of osmotic substance

increases in lens – lens hydration –swelling

- Amino acids are actively transported into cells – there are 3 different pumps for acidic ,basic and neutral amino acids

- The transfer of cations and amino acids occurs only at anterior surface by active transport and also inositol – active transport

- Glucose transport occurs by simple and facilitated diffusion

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• FACTORS MAINTAINING LENS TRANSPARENCY

-Regular arrangement of lens fibres – lamellar conformation

-Single layer of epithelial cells - Semipermeable lens capsule

- The relative dehydrated state of the lens- Avascularity of the lens

- High concentration of reduced glutathione in lens ---maintains lens proteins in reduced state -----ensures integrity of the cell membrane pump

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• CATARACTOGENESIS

• Factors implicated in Senile cataract

- Exposure to UV radiation

-Dietary factors

-Severe Diarrhoea

-Diabetes

-Renal failure

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• UV rays

• Absorbed by tryptophan

• Tryptophan N-Formyl kynurenine

• photosensitizatione and production of free radical oxygen

• Downregulation of Na/K ATPase

• Lens swelling and opacification

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• INCREASING AGE

• Decrease in pump reduced oxidative

mechanism reactions

Reversal of Na/K ratio decreased amino acids

Hydration of lens fibres decreased protein

synthesis

Denaturation of lens proteins Opacification of

cortical lens fibres

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• CHANGES IN CORTICAL CATARACT

- Progressive decrease in lens proteins and free amino acid

levels in lens

- Conversion of soluble proteins into insoluble proteins

- Decreased synthesis of lens proteins and increased protein

catabolism

- Decrease in the level of amino acids due to leakage

from disrupted membrane

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Alteration in electrolyte and water content of lens- water

content increases from immature to hypermature cataract• Sodium and calcium content of the lens ---INCREASES• Potassium content – DECREASES

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NUCLEAR CATARACT -Dehydration and compaction of nucleus - Increase in water insoluble proteins – Increases light scattering - Brown colour of lens – due to urochrome –absorbs light

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• ROLE OF GLUTATHIONE• Glutathione is made of –Glycine,cysteine and glutamic acid

• Most of Glutathione in lens is in reduced form GSH

2GSH +1/2 02 GSSG + H20

• GSH levels in cortex is higher than nucleus

• HMP Shunt pathway generates NADPH which maintains

glutathione in reduced state

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Lens proteins contain reduced sulfhydryl groups(PSH) and

oxidised disulfide groups (PSSP).

2PSH + GSSG 2GSH + PSSP

- Thus decreased GSH will result in PSH oxidation

alteration in protein linkages, transparency and their solubility

- Glutathione provides lens with a major detoxifying

mechanism via glutathione peroxidase

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• DIABETIC CATARACTS• 2 theories – 1) Sorbitol pathway and 2) Glycosylation pathway

1) Excess glucose is directed into sorbitol pathway

aldose reductase

Glucose Sorbitol

NADPH NADP

Sorbitol accumulates in lens Osmolarity of lens increases

NADPH is depleted Water content increases

Water clefts and vacuolesReduced GSH is depleted

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• Non enzymatic glycosylation of the lens proteins occurs

• Excessive glycosylation of lens capsule ------ increased fragility of lens capsule

• Structural changes in Enzymes,membrane proteins and crystallins in lens

GALACTOSEMIC CATARACT- Excessive Galactose Galactitol(Dulcitol)

in lens Aldose reductase- Galactitol accumulates and draws water

Water in lens fibres ruptures membranes and causes loss of K,Amino acids and Inositol

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• CATARACT DUE TO UVEITIS /INTRAOCULAR SURGERY / RETINITIS PIGMENTOSA

- In uveitis ----influx of plasma components into aqueous

- Following vitreo-retinal surgery ---breakdown of blood-vitreous barrier ----posterior subcapsular cataracts

- In RP – breakdown of the blood vitreous barrier by destruction of pigment epithelium.

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- Plasma phospholipids – Lysophosphatidyl choline and Lysophosphatidyl ethanolamine are implicated –they leak into the eye from ocular circulation.

- Two Unsaturated Fatty acids –Arachidonic acid and DHA are also implicated

- Macrophage oxidative enzymes can cause lytic effect by generation of peroxides

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• RADIATION CATARACT• -Ionising radiations – X rays,Gamma rays,Beta rays-

induce lens vacuoles and lens opacities

• Initially vacuoles appear in the equator and posterior subcapsular areas

• 3 mechanisms of damage by radiation

- Increased leakage of K,Inositol and glutathione

-Decreased incorporation of amino acids into proteins

- Arrest of cells entering mitosis and epithelial damage

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• CORTICOSTEROID INDUCED CATARACT

- Steroids induce abberant differentiation and migration of

epithelial cells

- Other mechanisms

- Elevation of glucose

- Inhibits Glucose -6-po4 dehydrogenase decreases NADH and

reduced glutathione

Inhibits Na/K ATPase

-Chemical modification of crystallins --- disulphide cross links between lens fibres----causes aggregation of lens fibres

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• PHYSIOLOGY OF ACCOMODATION• Accomodation is the ability to focus the diverging rays coming from a near

object onto the retina

• Nearest point at which objects can be seen clearly – Punctum proximum

• Farthest point –Punctum remotum

• Distance between these two points is called range of accomodation• The difference in Dioptric power needed to focus at near point and far point is

called amplitude of accomodation

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• MECHANSISMS OF ACCOMODATION• 3C s – Constriction of pupil , Convergence of the eyes

- Increase in Anterior curvature of lens

THEORIES OF ACCOMODATION

1.Relaxation theory(Hemhotlz theory/capsular theory)

- Most accepted theory worldwide .

-WHEN EYE AT REST WHEN EYE ACCOMODATES

Lens is compressed by

Capsule due to tension

of zonules

Due to relaxation of

the ciliary muscles

Contraction of ciliary muscle occurs

Causes ciliary ring to shorten and move the equator lens forward

Zonules are relaxed

Tension on capsule is relieved

Lens becomes more spherical

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• Other theories

2) Schahar ‘s Theory – Accomodation occurs when ciliary muscle contraction tenses the zonules

Lens stretches equatorially (coronally)

Only Central part of the lens bulges and moves anteriorly

According to this theory ,Presbyopia occurs due to a growth in the equatorial diameter of the lens with age

This in turn reduces the perilenticular space and hence ciliary muscle contraction can no longer tense the zonules

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• OCULAR CHANGES IN ACCOMODATION• -Slackening of zonules

• - Changes in anterior curvature of lens – radius of curvature decreases from 11 mm to 6mm

• - Anterior pole of lens moves forward

• Axial thickness of lens increases

• Constriction of pupil and convergence of eyes

• Choroid is stretched forwards and so is the ora serrata which moves forward by 0.05 mm

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• PATHOPHYSIOLOGY OF PRESBYOPIA

Presbyopia occurs due to- Changes in the elastic property of lens capsule- Sclerosis or hardening of the lens- Weakening of the ciliary muscle

Near point changes with age - 7cm at the age of 10 years- 25 cm at the age of 40 years- 33 cm at the age of 45 years- 50 cm at the age of 50 years

57THANK YOU