embryology and anatomy of human lens
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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
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