Embryology, AnAtomy And

Physiology of humAn lEns

HIRA NATH DAHAL

Lens

Lens (Lent-Latin word – lentil - similar shape) Transparent, avascular, biconvex, elliptical,

crystalline body Maintain clarity To refract light To provide accommodation

Embryogenesis of Lens

25th day of gestation optic vesicle forms and enlarges to oppose with ectoderm

Lens plate formation(27-29 days)

Lens pit

Lens plate27th –29th day of

gestation lens placode or lens plate is formed

Lens vesicle formation 30 days

Forming lens vesicle

Ectoderm

Lens vesicle completed 33 days

Embryonic nucleus formation (app. 40 days)

Primary lens fibers (app. 35 days)

35 – 40th day posterior epithelial cells º columnar cells º primary lens fiber (embryonic nucleus)

49th day (7th wk.) cells along the equator multiply & elongate to form secondary lens fibers (fetal nucleus)

Tunica Vasculosa Lentis

1st month of gestation hyaloid artery gives branch to the post. surface of lens(post. Vascular artery - PVA) - (Mittendorf ’s dot)

PVA anastomoses with choroidal vein (capsulopupillary portion)

It anastomose with long ciliary artery and form anterior vascular capsule (9th wk.) - (persistance pupillary membrane)

SUMMARY

Begins very early in embryogenesis

Days 25,optic vesicle forms from forebrain

Days 27,lens plate

Days 29, lens pit

Days 33, lens vesicle

Day35,primary lens fiber

7 weeks-Secondary lens fibers

Develop between 2-8 months: fetal Nucleus

8 weeks-y shaped suture

3rd month -Zonular fibers are secreted by the ciliary epithelium

Clinical Significance

Coloboma

Coloboma of iris Coloboma of choroid

Ocular associations

LenticonusPosterior

• Posterior axial bulge• Unilateral - usually sporadic• Bilateral - familial or in Lowe syndrome, Alports syndrome

Anterior

• Anterior axial bulge

• Associated with Alport syndrome

Small lens

• Small diameter • Small diameter and spherical• May be familial (dominant)

Microphakia Microspherophakia

• Systemic association - Lowe syndrome

• Systemic association - Weill-Marchesani syndrome

Ectopia lentis

SIMPLE( pupil may be normal)Pupil may be displaced in opposite direction (ectopia lentis et pupillae)

Congenital aphakia

Mittendorf’s dot

Peters’ anomaly

ANATOMY

Introduction

Lens is a biconvex, transparent crystalline structure. Adds 15-20 D of plus power to 43D created by cornea.(R.I

:1.386-1.41)

Avascular with no lymphatics, no innervation Accommodative power and color varies with the age Continually growing throughout life

Second major refracting unit of human eye

At birth, Weight:65- 90 mg Equatorial Diameter: 6.4 mm AP length: 3.5 mm

Adult lens, Weight-255 mg Equatorial Diameter: 9 - 10 mm AP length: 4.5-5mm

Radius of curvature: Ant surface-10 mm Post. surface -6mm

Morphology of the Lens

Biconvex its more convex posteriorly

Anterior surface – center is known as anterior pole

Posterior surface- center portion is called posterior pole

Optical axis (ap-pp) Equator (meeting point of as-ps)

Position of the Lens

Located between the iris and the viterous at the pupillary area in saucer shaped Patellar fossa and attached with vitreous by ligamentum hyaloideo-capsulare

Structure of Lens

1. Capsule

2. Epithelium

3. Cortex,nucleus

Structure Of The Lens:

Capsule: Elastic, transparent basement membrane surrounding the lens

completely created by epithelial cells anteriorly & cortical fibers posteriorly Thickest near the equator and thinnest at posterior pole Thickest basement membrane in the body.

Structure Of The Lens: (contd..)

Capsule: (contd..)

composed of glycoprotein associated Type IV collagen contains Heparan Sulfate (<1%) ⇒ maintains capsular

clarity

Functions: acts as a barrier in keeping back the vitreous as a barrier against fluorescein, bacteria, and

growth factors a source of antiangiogenesis factors

Capsule of the Lens

Basement membrane of the lens epithelium & thickest in the body

Elastic and transparent and are arranged in lamellae – type IV collagen

Along the equator –pericapsular membrane (zonular lamellae)

Epithelium: Single layer of cuboidal cells beneath the

anterior capsule have metabolic capacity-

to carry out all normal cell activitiesto generate sufficient ATP to meet the energy

needs

3 zones

a)central-cubical cells, stable, no mitosis

b)intermediate-cylindrical

c)germinative-columnar, forms lens fiber

Lens Fibers- after terminal differentiation of epithelial cells

increase in cell size/mass

loss of organelles (nuclei, mitochondria & ribosomes

Cortex

Nucleus

a)embryonic

b)fetal

c)infantile

d)adult

Lens Fibers

Highly organized concentric shells

Little extra cellular space 2 major components:

crystallin 90% & cytoskeleton

Zonule(suspensory Ligament)

Series Of Fine Fibres Passing Between The Ciliary Body And The Lens.

Transmit The Force From Ciliary Body To The Lens In Unaccomodated Eye.

Force Is Relaxed During Accommodation.

Fibres Consists Of Elastin Associated Glycoprotein Called Fibrillin Also Found In Vascular And Other Connective Tissues.

Weakness Leads To Subluxation Of The Lens As In Marfan’s Syndrome.

Fibres Arise From The Pars Plana And Ciliary Valleys Of Ciliary Body And Are Distributed To The Ant, Equatorial And Post. Parts Of The Lens Margin.

BIOCHEMISTRY AND PHYSIOLOGY OF LENS

Chemical Composition of Lens

Water 66 % of wet wt Protein 33 % of wet wt Lipids 28 mg/g of wet

weight Na+ 17 mmol* Cl 26 mmol K 125 mmol Ca 0.3 mmol

Glucose 0.6 mmol Lactic acid 14.0 mmol Glutathione 12.0 mmol Ascorbic acid 1.0 mmol Inositol 5.9 mmol pH 6.9*mmol/kg of H2O

Membrane

Very stable and rigid Lipids constitute 55 % of plasma membrane dry wt High content of saturated fatty acid High cholesterol:phospholipid ratio High concentration of sphigomyelin All contribute to tight packing of and low fluidity

Lens Lipid

Lipid constitute 1 % of total lens mass Cholesterol (50-60%) Phospholipid-sphingomyelin Gylcosphingolipids Functions: principal constituent of cell membrane

and associated with cell division

Lens Protein

33% of lens wet weight Majority in lens fibres 2 Major groups: a) Water soluble (80%) crystallin – alpha(32%), beta(55%) and

gamma(1.5%) b) Water insoluble 2 fractions soluble in urea – cytoskeleton protein insoluble in urea – MIP

32% β 55%γ 1.5%

Water Balance: 65% of wet weight

Closely associated with lens protein ∴ not freely diffusible

Intercellular water- determined largely distribution of monovalent cations (Na+, K+)

Biophysics:

lens absorbs light between 295 to 400 nm intrinsic fluorescence is due to-

phenylalanine tyrosine tryptophan (major)

extrinsic fluorescence is due to- chromophores- blue, green, yellow, orange, red

aberration - chromatic & spherical

Refractive Index

Peripheral cortex;1.386

Central nucleus ; 1.41

Anterior capsular surface more R.I than post. Surface

Higher the protein content, more the ref. Power

Transparency of Lens

Avascularity Highly ordered arrangement of macromolecular

components of lens cells and fibres Lamellar confirmation of lens proteins and minimal

intracellular space Small differences in refractive index between light

scattering components

Carbohydrate Metabolism

Energy production largely depends on glucose

Glucose enters both by simple and facilitated diffusion

Anaerobic glycolysis (80%) – 2 ATP Aerobic glycolysis by TCA Cycle (3%)- 36

ATP Pentose Phosphate Pathway (5-10%) –

provides NADPH and ribose Sorbitol Pathway ( <5% )

Sorbitol pathway

Glucose +NADPH+H+ Sorbitol +NADP+

Fructose +NADH+H+

Polyol dehydrogenase

Aldolase Reductase

High levels of sorbitol and fructose

Stimulation of HMP shuntIncrease in osmotic pressure

Indrawing of waterSwelling of fibers, disruption of cytoskeletal structures

Lens opacification

Sorbitol+NAD+

Glucose +NADPH+NAD+Fructose +NADP++NADH

DiabetesJuvenile

white punctate or snowflakeposterior or anterior opacities

May mature within few days

Adult

Cortical and subcapsular opacities

May progress more quickly than in non-diabetics

Galactose metabolism

Galactose +ATP Galactose-1-phosphate +ADP

UDP Glucose

UDP Galactose +glucose-1-phosphate

UDP glucose

Galactokinase

Galactose-1-phosphate uridyl transferase

UDP-galactose-4-epimerase

Galactitol

Increased osmolarity

Influx of water Osmotic damage to lens CATARACT

Protein Metabolism

Protein concentration is higher than in other tissues (33%)

Protein synthesis occurs throughout life Synthesis occurs mainly in epithelium and surface

cortical fibers

Oxidative Damage and Protective Mechanism

Free radicals are produced during cellular metabolism and by radiation

Free radicals lead to lens fiber damage Lens are equipped with protective enzymes such as

glutathione peroxidase, catalase, and superoxide dismutase

Vitamin C and E present in lens act as free radical scavengers

Maintenance of Lens water and Cation Balance

Critical to lens transparency Water content is approx. 66 % Intracellular Na 20 mM and K 120 mM Extracellular Na 150 mM and K 5mM Ca is maintained at 30 mM intracellular while

extracellular it is 2 mM Potential difference is maintained at -70mv

intracellularly

Pump Leak Theory

Combination of active transport and membrane permeability

Lens epithelium is site of active transport where Na/K ATPase and Ca ATPase are present

K and amino acid are actively taken by epithelium and diffuse out through back of lens

Na flows from back of lens and is exchanged actively with K in epithelium

Amino acids transport takes place by active transport dependent on Na gradient

Glucose enters lens by facilitated diffusion Waste products leave lens by simple diffusion

Pump-Leak Hypothesis:Na+150mMK+5mM

Na+20mMK+120mM

Inward active K+ transport

Outward active Na+ transport

Passive K+ diffusion

Passive Na+ diffusion

ANTERIORAqueous humor

POSTERIORVitreous humor

Passive Diffusional Exchange of H2O and solutes

Inward active A.A pumps

Passive leakH2O and solutes

Epithelium

Calcium (30 mM): Homeostasis maintained by Ca2+-ATPase

oLoss of Ca metabolism can be damaging to lens metabolism.o ed Ca levels leads to depressed glucose metabolism, formation of high mol.wt protein aggregates and activation of destructive proteases. ed levels of calcium may lead to cataract formation.

Accommodation

Mechanism by which eye which changes focus from distant to near focus

Occurs by change in shape of lens mainly in anterior lens surface by action of ciliary muscle

Relaxation theory is the widely accepted theory of accommodation

12-16 D in adolescence, 4-8 D at 40 years, <2 D after 50 years

Age Related Changes

Morphological Changes:-

↑ in both the mass & dimension of the lens

epithelial cells- becomes flatter & density ↓es

lens fibers- total loss or partial degradation of a no. of plasma membrane & cytoskeletal proteins

cholesterol:phospholipid ratio ↑es

lens capsule- thickens throughout life (collagen type IV vs. I, III, IV)

6 months 8 yrs 12 yrs

25 yrs 47 yrs 60 yrs

70 yrs82 yrs

91 yrs

70 yrs brown NS

60 yrs withCortical cataract

Mixed NS + cortical

Age Related Changes

Physiological Changes:- membrane potential- from –70mV (at age of 20 yrs) to –

20mV (at the age of 80 yrs)

sodium concentration - ↑es

Na+:K+ permeability ratio ↑es by six fold

free calcium level ↑es

Age Related Changes

Biochemical Changes:- overall metabolic activity of the lens ↓es

↓ glycolytic activity

↓ level \ activity of antioxidants

Changes in Crystallins:- molecular accumulation of high weight aggregates

↑ed insolubility