lens

Sanket Parajuli

EMBROYOLOGY OF LENS At about 25 days of gestation, 2 lateral evaginations from the forebrain

called optic vesicle . ---As optic vesicle enlarge they become closely apposed to the surface ectoderm

Lens placode • The cells of the surface ectoderm that overly the optic vesicle

become columnar at about 27days of gestation. This thickened cells is called lens placode

Lens pit• It appears at 29 days of gestation as a small indentation of the

lens placode

Lens vesicle• As the lens pit continues to invaginate, the stalk of cells that

connects it to the surface ectoderm constricts and eventually disappears. The single layer of cuboidal cells encased within a basement membrane is called lens vesicle

• The posterior cells of the lens vesicle become more columnar and begin to elongate. This elongated fiber is called primary fibers• The primary lens fiber make up the embryonic nucleus• The cells of the anterior lens vesicle do not change. This monolayer of

cuboidal cells is called lens epithelium

Secondary lens fibers• At about 7 weeks of gestation the cells of the

lens epithelium in the area of equator begin to multiply and elongate to form secondary fibers. This make up fetal nucleus.

Lens sutures• As lens fiber grow anteriorly and posteriorly

a pattern emerges where fibers meet and interdigitate… This pattern are called suture• an erect Y-suture appearing anteriorly and an

inverted Y-suture posteriorly

Congenital anomaliesCongenital aphakia::if lens placode fails to form

Lenticonus:--the localized cone shape deformation of anterior or posterior surface.

Lentiglobus: the localised deformation of the lens surface is spherical.

Lens coloboma: • primary (a wedge shaped defect of lens periphery) • secondary(a flattening of lens periphery caused by the lack of

ciliary body or zonular development)

Microspherophakia: the lens is small in diameter and spherical

• Remnants of tunica vasculosa lentis may persist at the posterior lens capsule as Mittendorf's dots

LENS• transparent, biconvex, elliptical, avascular body of

crystalline appearance • Transparent-- allow passage of incident light and• Elastic-- to facilitate changes in shape accommodation

Anatomical RelationAnterior : • Anterior chamber of the eye

through the pupillary aperture • posterior surface of the iris

Lateral : • Posterior chamber of the eye • zonules through ciliary

processes

~3 mm

Anatomical Relation

Posterior: • Vitreous, separated by slit like

Retrolental/Berger’s space filled with aqueous and

• attached to vitreous in a circular fashion by ligamentum hyaloideocapsulare (Wiegert’s ligament)

~3 mm

• The lens is unique among organs in that it contains cells solely of a single type, in various stages of cyto differentiation, and retains within it all the cells formed during its lifetime

• oldest cells --core or nucleus of the lens, • new cells--superficially to the cortex, in a series of concentric layers

Equatorial diameter of the adult lens is 9-10 mm. • Axial sagittal width = 3.5 mm at birth, 4

mm at 40 years increases slowly to 5.0 mm in extreme old age

• Equatorial diameter is 6 mm at birth, 10 mm in the second decade and changes little thereafter

• Like all lenses has i. two surfaces, anterior and posterior, and ii. a border where these surfaces meet, known as the equator (equator

lentis) • Anterior surface, less convex than the posterior • The center of the anterior surface is known as the anterior pole, and is

about 3 mm from the back of the cornea• The posterior surface, more curved than the anterior, presents a radius

of about 6 mm

• Refractive index of the lens =1.39• The dioptric contribution of the lens is about 15 out of a total of about 40 diopters for the

normal eye (non accommodative state• At birth the accommodative power is 5-16 diopters, diminishing to half of this at about 25

years of age and to 2 diopters or less at age 50 years.

• With the pupil dilated+ slit-lamp microscope + slit-beam a stratification of the lens into concentric layers ::From the front backwards are:,

A)superficial cortexi. capsule; ii. subcapsular clear zone (cortical zone—c1α); iii. a bright narrow, scattering zone of discontinuity(c1ß) ; iv. the subclear zone of the cortex(c2)

B) 2 deep cortical or perinuclear zones which autofluoresce a brilliant green under blue exciting lightv. first of these zones (C3) is a bright, scattering zone vi. second is relatively clear (C4). C)Nucleus represents the prenatal part of the lensshows further stratification, with central clear interval which has been termed the 'embryonic' nucleus

STRUCTURE

The lens consists of 1. the lens capsule;2. the lens epithelium;3. the lens cells or fibers.

lens capsule

• completely envelops the lens

• Capsule is basement membrane of lens epithelium & is the thickest BM in body

• It is much thicker in front than behind (equator>poles)

• Capsule receives the insertion of the zonular fibers anteriorly and posteriorly at the lens periphery as well as at the lens equator

• Under the light microscope the capsule appears transparent, homogeneous

• has lamellar structure

• There are up to 40 lamellae, each of which is about 40 nm thick

• The lamellae run parallel to the capsular surface

• lamellar structure disappears from the posterior pole during the first decade and from the anterior aspect four or five decades later

• 90% of the age-related losses in accommodation result from changes in capsular elasticity & that the loss of lamellae may be a morphological manifestation of this process

• The capsule is freely permeable to low molecular weight compounds but restrict large colloidal particles (eg albumin)

Applied::

• Thinness of the posterior capsule creates a potential for rupture during ECCE

•Moulds the shape of lens during accommodation

True Exfoliation• Superficial zonular lamella of the capsule splits

off from the deeper layer• Exposure to infrared radiation

PsedoExfoliation• Basement membrane-like fibrillogranular white

material deposited on the lens, cornea, iris, anterior hyaloid face, ciliary processes, zonular fibers and trabecular meshwork

Voissius Ring• Imprinted iris pigments in the

anterior surface of anterior lens capsule due to blunt trauma to eye

Voissius ring

• The lens epithelium

consists of a single sheet of cuboidal cells Lies deep to the capsule and extending outwards to the equator

Its cells are cuboidal in sagittal section, but polygonal in surface view There is no corresponding posterior layer because the posterior epithelium of the embryonic lens is involved in the formation of the primary lens fibers which come to occupy the center of the lens nucleus

Central zone• The central zone represents a stable population of cells whose numbers, like those of

the corneal endothelium, slowly reduce with age• Normally no mitoses• Mitosis occurs in response to insults eg: uveitis• Metaplasia of these central zone lens epithelial cells—leads to—anterior sub-capsular

cataract like shield cataract in atopic dermatitis and glaucomflecken after ACG attack• lies in line of pupillary aperture

Intermediate zone• peripheral to the central zone and its cells are smaller, more cylindrical and with a

central nucleus• Theses cells mitose occasionally

Germinative zone

• most peripheral and is located Just pre equatorially • major site of cell division • Actively dividing to from new cells-migrate posteriorly to form lens

fibers• Extremely susceptible to radiation• Dysplasia of these transitional zone cells can lead to PSCC as in

radiation cataract, myotonic dystrophy and NF2

• The germinative zone, unlike the central zone, is protected from the potentially harmful effects of radiant energy in UV range, 300-400 nm (e.g. sunlight) by its location behind the iris

FUNCTIONS

• The epithelium contains Na/K ATP ase & calmodulin dependent Ca++ activated ATPase for the active transport of electrolytes

•Active transport mechanism for amino acid

• Regulates the transport of metabolites, nutrients & electrolytes to lens fibers from AH

• Secretion of capsular material

Applied Anatomy

•Germinative cells left behind after ECCE can give rise to posterior capsular opacification as a result of aberrant proliferation and cell migration

Lens fibers:

• Epithelial cells elongate to form lens fibers• Initially anterior epithelial cells elongate to form fibers• Later derived from equatorial region of anterior epithelium

Fiber elongation

• Following terminal cell division, one or both daughter cells pass into the adjacent transitional zone, in which the cells are organized into meridional rows

• They differentiate into secondary lens fibers, rotating through 180° and elongating anteriorly and posteriorly

• New lens fibers retain their polarity, so that the posterior (basal) part of the fiber remains in contact with the capsule (basal lamina) while the anterior (apical) part is separated from it by the epithelium

• the parallel organization of the meridional rows is achieved

• Continued alignment of fibers is achieved by intralenticular tension and the cell pressure of contiguous fibers

• Loss of meridional row arrangement is associated with cataract

• Epithelial mitosis is accompanied by DNA synthesis, while fiber elongation involves increased transcriptional activity and RNA synthesis

LENS FIBERS• It is the main mass of the lens

• Fibers are formed by multiplication & differentiation of epithelial cells at the equator

• Each elongated lens cell is called lens fiber

•As the cells elongate anteriorly --nucleus move anteriorly+deep

• this produces the nuclear pattern known as lens bow

• They are U shaped ,runs meridionally from posterior to anterior lens surface

• Earliest formed fibers are in center– nucleus, later formed fibers form the outer—

cortex of lens

• Earliest formed fibers in center –embryonic nucleus which is followed by fetal nucleus

• Fibers formed after puberty is adult nucleus

•Division of lens

Fetal nucleus:• From 3 months of gestation till birth. • Fibers meet around sutures which are

anteriorly Y-shaped and posteriorly inverted Y-shaped

Infantile nucleus:• corresponds to the lens from birth to puberty

Adult nucleus :• lens fibers formed after puberty to rest of the

life

• The primary lens fibers make up the embryonic nucleus

• Fetal nucleus: 2ndary lens fibers from 2-8 mnth of gestation

• Infantile nucleus : 2ndary lens fibers during last weeks of fetal life to puberty

• Adult nucleus : 2ndary lens fibers after puberty

• Cortex consists of recently formed superficial secondary lens fibers

• Initial fibers forming fetal nucleus surrounding embryonic nucleus are arranged in pattern (erect Y shape anteriorly ,inverted Y posteriorly)

• Later in gestation and after birth --complicated suture patterns are formed

• The lens fibers have few vesicles, microfilaments, microtubules & mitochondria in their cytoplasm

• Lens fibers are tightly packed –little intercellular space.

• Fibers are held together by interlocking processes (ball & socket interdigitations) and (tongue and groove interdigitations)

• These interlockings help in molding of lens during accommodation

•During development lens fiber cells lose their nuclei & cytoplasmic organelles—produce intracellular protein—k/a cystallin (alpha & beta)—which constitute 60% of lens fiber mass

•High refractive index of lens—crystallins

Water insoluble proteins

1) Alpha crystallin• Largest crystallin• Accounts for 31% total lens protein

2) Beta crystallin • Most abundant crystallin, accounts for 55% total lens protein• Most heterogenous group

3) Gamma crystallin• Smallest crystallin• Least abundant-2%

Applied Anatomy

•High refractive index of the lens results from the high concentration of crystallins

• Zones of demarcation (as seen through Slit-lamp) occur because strata of epithelial cells with differing optical densities

COMPOSITION OF LENS

• Lens contain high protein & low water

Transparency of lens:

• Single layer of epithelial cells • Semipermeable character of the lens capsule• highly packed nature of cells• Characteristic arrangement of lens fiber• Pump mechanism of the lens fibers•Avascularity of lens• high concentration of reduced glutathione in the lens

maintain the lens protein in a reduced state

Takes nutrients from two sources by diffusion

1. Aqueous humour (main source) 2. Vitreous humour

LENS METABOLISM: Carbohydrate Metabolism

• In the lens energy production depends on metabolism of glucose• Glucose enters the lens by simple diffusion• Glucose transport take place across both surfaces of lens lens has a specific glucose transporter • Epithelial cells- GLUT-1• Lens fiber cells- GLUT-3

• Glucose is rapidly metabolized in lens so that the level of free glucose in lens is less than that of in aqueous humor• More than 70% of glucose is metabolized anaerobically by glycolytic

pathway• Small portion of glucose is metabolized by kreb’s cycle

GLYCOLYSIS

•More active than other pathway• In anaerobic glycolysis 1 mole of glucose is metabolized to generate

2 molecules of ATP•When excess glucose is present it enters the sorbitol pathway

• Lens is unable to survive without glucose, even in the presence of oxygen, when endogenous glucose sources are consumed –there’ll be alteration of cytoplasmic composition of lens, cellular deterioration and loss of transparency occur

Aerobic metabolism of glucose

• Production of ATP in lens via Krebs Cycle is limited to epithelium

•Aerobic metabolism of glucose is more efficient than glycolysis—it produces 36 ATP from 1 molecule of glucose.

•Only about 3% lens glucose is metabolized, Produces 25% of lens ATP

• C02 produced by Krebs cycle enters aqueous humor by simple diffusion

HEXOSEMONOPHOSPHATE (HMP) SHUNT • Lens also metabolizes glucose via HMP shunt•Approximately 5% lens glucose is metabolized• It doesn’t generate large quantity of ATP but is important source of

NADPH –require for sorbitol pathway

• Pathway stimulated by elevated level of glucose, linked to sugar cataract• Carbohydrate product of HMP shunt enter the glycolytic pathway and

are metabolized to lactate

SORBITOL PATHWAY

• Play a pivotal role in development of sugar cataracts• Less than 5% of lens glucose is normally converted to sorbitol•Glucose is converted to sorbitol by enzyme aldose reductase then to

fructose by polyol dehydrogenase

•When glucose level increases—Sorbitol pathway activated—Sorbitol accumulates within the cells of the lens—cell membranes are impermeable to sorbitol –sets up an osmotic gradient that induces influx of water & result in lens swelling & loss of lens transparency

Glucose metabolism in lens

Oxidative Damage And Protective mechanisms:

•Highly reactive free radicals ( generated in course of normal cellular metabolic activities) can lead:•Damage to lens fibers and DNA•Attack the proteins and membrane lipids in the cortex

Enzymes in lens that protects against free radicals:•Glutathione perioxidase• Catalase• Superoxide dismutase•Vitamin E and Ascorbic acid

WATER & ELECTROLYTE BALANCE

• Lens physiology is the mechanism that controls water & electrolyte balance which is critical to lens transparency

•Normal human lens contains 66% water & 33% protein –this amount changes with aging

• The lens cortex is more hydrated than lens nucleus

• Sodium concentration in lens—20mM & Potassium concentration—120mM,these levels in surrounding aqueous & vitreous humor are different (Na is about 150mM,K is 5mM )

LENS EPITHELIUM• Lens is dehydrated—has higher level of K ions & amino acids than the

surrounding aqueous & vitreous

• Lens contain lower level of Na+, Cl- & water than the surrounding environment

• Cation balance between inside & outside of lens-- –is the result of both permeability properties of lens cell membrane & activity of sodium pumps

(Na+ K+ ATPase)

• Na+ pump act by pumping Sodium ions out while taking Potassium ions in—regulated by enzyme Na+ K+ ATPase.

PUMP LEAK THEORY

• Combination of active transport & membrane permeability –is pump leak system of lens

• Na+K +ATP ase activity is found in lens epithelium

• Epithelium is primary site for active transport in the lens

• K is pumped into lens & Na is pumped out in anterior surface –chemical gradient is generated—stimulates the diffusion of Na into lens & K out of the lens via posterior surface—PUMP & LEAK

• K concentrated in anterior lens ,Na concentrated in posterior lens

• Unequal distribution of electrolytes across the lens cell membranes result in electrical potential difference between inside & outside of lens.

• The inside of lens is electronegative about -70mv, there is -23mv potential diff between anterior & posterior surfaces of lens.

• The normal potential difference of about 70mv is altered by changes in pump activity or membrane permeability.

Calcium homeostasis• Intracellular level of calcium in lens is approximately 100 mM whereas

exterior calcium level is 1 mM

• This large transmembrane calcium gradient is maintained by calcium pump (Ca+ ATPase)

• Lens cell membrane are impermeable to calcium

• Increase level of Calcium –cytotoxic in lens—cataract

•Amino acid:

•Amino acid transport take place in anterior epithelium

•AA transport in lens depend upon Na+ gradient generated by Na/K ATP ase

•Ascorbic acid, myo-inositol, choline have specialized transport mechanism in the lens

AGE CHANGES IN THE LENSPhysical changes lens weight and thickness-increases light transmission – decreases light scattering - increase refractive index- increases

Metabolic change-most metabolic changes decreases

Changes of plasma membrane and cytoskeleton1. loss of hexagonal cross-section of fiber cells2. Age related losses of membrane proteins and lipids3. Loss of membrane potential

Cataractogenesis:

•Occurrence of optical discontinuity in lens to a magnitude to cause noticeable dispersion of light

•Oldest concept:Due to precipitation, agglutination, denaturation or coagulation of soluble lens protein

Biochemical changes have been studied extensively

Senile cataract:

usually b/l but one eye affected earlier than the otherOccurs in 2 forms:• Cortical—soft cataract• Nuclear—hard cataract

Risk factors for cortical cataract:a) Exposure to UV light:• UV radiation(290-320 nm)---absorbed by tryptophan—gets converted to N-formyl-

kynurenine—this acts as photosensitizer—produces free radical—O2 free radical downregulates Na/K ATPase---lens swelling and opacificaton

• Free radicals generated: H2O2 –down regulates Hexokinase

Nuclear cataract:

• There’s intensification of age related nuclear sclerosis

• There’s dehydration and compaction of nucleus

• Increase in water insoluble proteins however, total protein content and distribution of cations remain normal

• There may be deposition of pigments melanin/urochrome derived from AAs

Role of Glutathione:• Superoxide radicals may be the most toxic to lens proteins• Lens ascorbate –acts as scavenger of the superoxides—ascorbic acid

converts superoxide to less reactive H2O2

• Reduced levels of glutathione/ascorbates—accumulation of free radicals

Glutathione levels fall due to:• Decrease in synthesis(aqueous has low levels of glutathione)• Relative deficiency of glutathione reductase

• Sugar cataract: involves cataract due to galactosemia and juvenile diabetes

Galactosemic cataract::• Classical galactosemia—due to deficiency of galactose 1 PO4• Also related is Galactokinase deficiency• Frequently B/l – associated with oil droplet central lens opacity• Changes may be reversible and can be prevented by eliminating milk and

milk products

• Pathogenesis of sugar cataract:

1. Sorbitol, aldose reductase and osmotic hypothesis:

excess glucose---------aldose reductase converts it into------sugar alcohol (glucose sorbitol/galactose dulcitol)-----------this is unable to escape lens + its not metabolized-------------cytoplasm hypertonic-------------H2O into lens+ alteration of Na/K ratio ------swelling of lens-----disruption of lens architecture-------formation of foci of light scattering --opacity

2. Hypothesis of autooxidation of sugars:• Suggested by some • Some disregard as significant amount of autooxidation has not been

established

3.Theory of non enzymatic glycosylation:More important than other theoriesInitial reaction is the attack of open chain form of sugar on amino groups of lens proteinsInitial attack leads to variety of chemical entities and induces structural changes to enzymes ,membrane proteins and crystallines in the lens

Radiation cataract:Damage to germinative zone of lens epithelium

Infrared(heat) cataract:: Prolonged exposure to infrared—discoid posterior subcapsular cataract(glass worker’s cataract)

Irradiation cataract:Ionising radiation(X rays, Y rays)Latent phase(6mths to few years)

Mechanism:

Radiation::increase membrane permeability----affect metabolism and synthesis of protein and cell division---Alterations in glutathione+ RNA metabolism also occurs

Corticosteroid induced cataract:

• PSCC associated with both oral and topical corticosteroid use

Steroids can result in cataract by :• Elevation of glucose• Inhibition of Na/K ATPase• Increased cation permeability• Inhibition of RNA synthesis• Inhibition of G6PD• Loss of ATP

SUSPENSORY LIGAMENT OF LENS (Zonules)

• Arise from basal laminae of non-pigmented epithelium of ciliary body

• Inserts in a continuous fashion, on the lens capsule in the equatorial region

• Fibers are 5-30 μm in diameter

Structure:• Zonular fibers are transparent stiff and non elastic• Composed of glycoproteins and mucopolysaccharides• Susceptible to hydrolysis by alpha-chymotrypsin

Grossly:• They form a ring of fibers that extends from ciliary body

to equator of lens• On c/s—ciliary zonules appear arranged in triangular

fashion• Space between triangle filled with zonular fibers except

at the space near equator of lens k/a canal of Hannover

• Main fibers of ciliary zonules:Orbiculo- posterior capsular fibers• Most posterior, and innermost fibers• Origin- ora serrata• Passes anteriorly in close contact with anterior

limiting layer of vitreous• Inserts together with hyalocapsular ligament in

posterior capsule of lens

Orbiculo – anterior capsular fibres• Thickest and strongest• Origin: pars plana of ciliary body (orbicularis

ciliaris)• Courses anteriorly• Inserts anterior to equator, in sides of ciliary

process

Cilio –posterior capsular fibres • Most numerous• Origin mainly from valleys of ciliary processes• Courses posteriorly• Inserts in posterior capsule, anterior to

Orbiculo- posterior capsular fibres

Cilio – equatorial fibres • Arises from valley of ciliary process• Passes directly inwards• Inserts at the equator

• Fibers arise from the non pigmented epithelium of Ciliary Body and are distributed

1) as the Anterior fibers:arising from pars plana and anterior part of ora serrata pass anteriorly to get inserted anterior to the equator.

2) as the Equatorial fibers:fibres passes from the summits of the ciliary processes almost directly inward to be inserted at the equator

3) as Posterior fibers: The fibres originating from comparatively anteriorly placed ciliary processes pass posteriorly to be inserted posterior to the equator

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

Applied Anatomy

• In Marfan syndrome ,mutation in the fibrillin gene lead to weakning of the zonule and subluxation of the lens.

75

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 accommodation• The difference in Dioptric power needed to focus at near point and far point is called

amplitude of accommodation

MECHANSISMS OF ACCOMODATION• 3C s • Constriction of pupil• Convergence of the eyes • Increase in Anterior curvature of lens

THEORIES OF ACCOMODATION 1.Relaxation theory(Hemholtz theory/capsular theory) - Most accepted theory worldwide .WHEN EYE AT REST Lens is compressed by Capsule due to tension of zonules

WHEN EYE ACCOMODATES

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

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

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

80

• 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

References:• Wolff’s anatomy of eye• Snell’s anatomy of the eye and orbit• AAO• Internet sources

Cataractogenesis:

•Occurrence of optical discontinuity in lens to a magnitude to cause noticeable dispersion of light

•Oldest concept:Due to precipitation, agglutination, denaturation or coagulation of soluble lens protein

Biochemical changes have been studied extensively

Senile cataract: usually b/l but one eye affected earlier than the other• Occurs in 2 forms:• Cortical—soft cataract (cuneiform/cupuliform)• Nuclear—hard cataractRisk factors:a) Heriditaryb) Exposure to UV light:• UV radiation(290-320 nm)---absorbed by tryptophan—gets converted

to N-formyl-kynurenine—this acts as photosensitizer—produces free radical—O2 free radical downregulates Na/K ATPase---lens sweling and opacificaton

• Free radicals generated: H2O2 –downregulates Hexokinase

C. Dietary factors: protective effect with high serum leb=vels of carotenoids, precursors for vitamin A and vitamin DSelenium is found to be a risk factor

D. Severe diarrhea/dehydration

E. Diabetes

F. Renal failure—high blood urea level has been found in patients witrh cataract

G. Hypertension

H.Myopia

Biochemical changes:• There’s progressive decrease in lens protein and free Aas + alteration

of electrolytes and water content• Water content:Increases from immature cataract(70%) to hypermature(morgagnian stage)(80%)Most water responsible for hydration is extralenticular but hydration also occurs from bound water from conformationally altered proteins

Protein:Total protein content is decreased with maturation of cortical senile cataractBut water insoluble fraction of protein increases

Decrease of soluble proteins occurs due to:• Leakage of LMW proteins form lens• Conversion of proteins to insoluble state• Decreased synthesis of lens proteins• Increased protein catabolism

Loss of αA crystalline and loss of ÝS crystalline

• Free Aas:• Decrease in levels of free AA have been found with maturation of

cortical cataract

• Sodium content progressively increases and potassium levels decrease with maturation of cataract

• Calcium content: increases with maturation of cataract

Nuclear cataract:• There’s intensification of age related nuclear sclerosis• There’s dehydration and compaction of nucleus• Increase in water insoluble proteins however, total protein content and

distribution of cations remain normal• There may be deposition of pigments melanin/urochrome derived

from AAs

Role of Glutathione:• Superoxide radicals may be the most toxic to lens proteins• Lens ascorbate –acts as scavenger of the superoxides—ascorbic acid

converts superoxide to less reactive H2O2

• Reduced levels of glutathione/ascorbates—accumulation of free radicals

Glutathione levels fall due to:• Decrease in synthesis(aqueous has low levels of glutathione)• Relative deficiency of glutathione reductase

• Sugar cataract: involves cataract due to galactosemia and juvenile diabetes

Galactosemic cataract::• Classical galactosemia—due to deficiency of galactose 1 PO4• Also related is Galactokinase deficiency• Frequently B/l – associated with oil droplet central lens opacity• Changes may be reversible and can be prevented by eliminating milk and

milk products

• True diabetic cataract: snow flake cataract/snow strom cataract

• Initially a large number of fluid vacuoles appear underneath anterior and posterior capsule----b/l snow flake opacities in cortex

• Pathogenesis of sugar cataract:

1. Sorbitol, aldose reductase and osmotic hypothesis: excess glucose---------aldose reductase converts it into------sugar alcohol (glucose sorbitol/galactose dulcitol)-----------this is unable to escape lens + its not metabolized-------------cytoplasm hypertonic-------------H2O into lens+ -alteration of Na/K ratio ------swelling of lens-----disruption of lens architecture-------formation of foci of light scattering --opacity

2. Hypothesis of autooxidation of sugars:• Suggested by some • Some disregard as significant amount of autooxidation has not been

established

3.Theory of non enzymatic glycosylation:More important than other theoriesInitial reaction is the attack of open chain form of sugar on amino groups of lens proteinsInitial attack leads to variety of chemical entities and induces structural changes to enzymes ,membrane proteins and crystallines in the lens

Changes range from:• Conformational changes—thiol oxidation—aggregation,formation of

disulphide bonds +inactivation of enzymes• Flow chart khurana

• Radiation cataract:Damage to germinative zone of lens epithelium

Infrared(heat) cataract:: Prolonged exposure to infrared—discoid posterior subcapsular cataract(glass worker’s cataract)

Irradiation cataract:Ionising radaiation(X rays, Y rays)Latent phase(6mths to few years)

Mechanism:

Radiation::increase membrane permeability----affect metabolism and synthesis of protein and cell division---Alterations in glutathione+ RNA metabolism also occurs

Fig khurana

Corticosteroid induced cataract:• PSCC associated with both oral and topical corticosteroid use• Steroids—induce aberrant differentiation and migration of epithelial cells

leading to posterior opacification• Typical glucocorticoid receptors are present in lens—lens tissue can form

glucuronide and sulphate conjugates of cortisol

• Steroids can result in cataract by :• Elevation of glucose• Inhibition of Na/K ATPase• Increased cation permeability• Inhibition of RNA synthesis• Inhibitin of G6PD• Loss of ATP

• AGEING OF THE ZONULE The fetal and infantile zonular fibres are finer and less aggregated than in the adult, and richer in proteoglycans. In the elderly, the fibres are finer and more sparse, especially the meridional ones, and they rupture more readily (Buschmann et al., 1978; eale, 1982). In the first two decades of life the zonular attachments are narrow. With time they broaden and move more centrally, both anteriorly and posteriorly. Anteriorly, the zonule-free area of the capsule reduces from 8 mm at age 20 years, to 6.5 mm in the eighth decade or as low as 5.5 mm, so that the insertion may intrude into the region selected for capsulotomy during extracapsular cataract surgery (Farnsworth and Shine, 1979; Stark and Streeten, 1984) (Fig. 12.48). In childhood, the anterior hyaloid membrane is closely attached to the whole posterior zonular insertion and the lens. In the adult, the anterior hyaloid membrane may be peeled back to the zonular insertion, its strongest point of attachment at all ages. During intracapsular extraction a superficial flap, or even the full thickness of lens capsule,may be separated by this attachment, the posterior zonular complex and the circumferential complex (see below). During intracapsular cataract extraction most of the zonular complex is torn from the capsule, with only the tips of the anterior zonular insertions and a fewmeridional fibres remaining. The zonule may also tear partially, during extracapsular cataract surgery, with rupture, or a preferential separation of the posterior and meridional fibres from the capsule. About 5% of these dehiscences may be detected at the time of surgery, occurring during the removal of lens material as traction is applied to the zonule

• More are identified at postmortem • The zonule is weak in the disorder pseudoexfoliation of the lens

capsule, and is four times more likely to rupture during cataract surgery than normally • Each zonular bundle associated with a major ciliary process forms a

unit which emerges as a flat ribbon of bundles 6-10 per ciliary unit. It has been suggested that rubbing of the posterior iris across the zonule is responsible for iris pigment loss in pigmentary glaucoma