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LENS-ANATOMY
 AND
 PHYSIOLOGY




VISHNU NARAYANAN M.R
ANATOMY
1. Gross anatomy
• Biconvex, transparent, crystalline structure
• Ability to change shape
• divides eye into anterior and posterior segments
• 2 surfaces-anterior and posterior




   8/25/2012                                         2
ciliary body

              Zonules

                  Lens


              Zonules

            ciliary body


8/25/2012                  3
Position




8/25/2012   4
LOCATION OF LENS




8/25/2012          5
DIMENSIONS OF LENS



             10 mm   6 mm




 8/25/2012                  6
Histology of lens




8/25/2012           7
A)Capsule
• Acellular elastic structure
• basement membrane -type 4 collagen+sulphated GAG
• Variable thickness
• Zonules run from ciliary processes and fuse onto outer
  layer of capsule
• Main function is to mold the shape of the lens in
  response to tension from zonules




8/25/2012                                             8
B)Anterior epithelium

• Single layer of nucleated epithelial cells interconnected with gap
    junctions and desmosomes
• The only metabolically active part of lens
• Functionally divided into 2 zones-
i] Pre-equatorial zone- columnar cells
              Actively dividing and differentiating into lens fibers
ii]Central zone-cuboidal cells
              i) Transports solutes between lens and aqueous
              ii) Secretes capsular material
• Maintains the osmotic balance of lens

   8/25/2012                                                    9
C)Lens substance

• Composed of lens fibres
• Consist of primary and secondary fibers
• Produced by mitosis of epithelial cells in the pre-
  equatorial zone
• They elongate and undergo differentiation with
  pyknocytosis and eventual loss of cell oraganelles
  and nucleus
• This is an important factor in the transparency of
  the lens

8/25/2012                                               10
• As lens fibres elongate and new ones form, the older
  ones are pushed towards the depth of the lens
• Lens bow-shifting of lens nuclei forms a visible line in
  the equator
• Fibres are arranged in zones in which fibres growing
  from opposite directions meet in sutures
• Consist of nucleus and cortex




8/25/2012                                                11
LENS FIBRES-PHOTOMICROGRAPH




8/25/2012                     12
8/25/2012   13
8/25/2012   14
Cortex

• Youngest lens fibres
• It is located peripherally, and is
  composed of secondary fibres formed
  continuously after puberty




8/25/2012                               15
Nucleus

•   Central part with oldest fibres
•   Dense and compactly arranged lens fibres
•   Higher refractive index than capsule
•   Different zones depending on period of development




8/25/2012                                            16
epinucleus

8/25/2012                17
8/25/2012   18
Anterior Suture   posterior suture
( erect Y )
                    inverted Y




  8/25/2012                   19
Sutures




8/25/2012   20
Zonules of zinn
• Suspensory ligaments/ciliary
  zonules

• Series of fibres from ciliary
  process

• Holds the lens in position

• Assist action of ciliary muscle

• Attached to lens capsule at
  zonular lamella
   8/25/2012                        21
Parts of ciliary zonules




8/25/2012                  22
Types of zonules




8/25/2012          23
Zonular spaces




8/25/2012        24
EMBRYOLOGY

1)Formation of lens vesicle
• 4 weeks
• Optic vesicle induces lens placode from
  ectoderm
• Lens placode invaginates and becomes lens pit
• Optic vesicle also invaginates and becomes
  optic cup
• Lens pit separates from ectoderm to become
  the lens vesicle
8/25/2012                                     25
8/25/2012   26
2)Formation of lens fibers and zonules

• Primary lens fibres—fibres formed upto 3rd month
  Cells in posterior portion of lens vesicle elongate to fill vesicle
   forms emryonic nucleus
• Secondary lens fibres—3rd month to entire life
  Cells in anterior portion of vesicle divide actively and elongate
  includes all other nucleus

• Lens capsule-produced by anterior epithelial cells
• Lens zonules—from neuroectoderm in ciliary area(3rd – 5th month)
• Tunica vasculosa lentis--nourishment to embyonic lens
                           branch of hyaloid artery
                           disappears before birth
 8/25/2012                                                              27
PHYSIOLOGY OF LENS

COMPOSITION




8/25/2012            28
LENS PROTEINS
Water soluble lens crystallins
• 90% of total lens protein
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, 6 distinct subgroups
3) Gamma crystallin
• Smallest crystallin
• Least abundant-2%

Water insoluble proteins
• Insoluble albuminoids-12%
8/25/2012                                                         29
WATER

• Lens –dehydrated state
• Unique arrangement of proteins within lens fibres
• Low protein osmotic activity within lens
• Tightly packed fibres with minimum extracellular spaces
• Lens epithelium transports water into the fibre mass
• Half of the water -protein hydration
• Water excreted via aquaporin in the equator into
  aqueous
• Important factor maintaining lens transparency

8/25/2012                                                   30
Electrolytes
• Active transport of ions and low molecular weight metabolite
  takes place between lens and aqueous humour
• Epithelium contains Na-K-ATPase and a calmodulin-
  dependent Ca-activated ATPase for the active transport of
  electrolytes
• Fibre cells contain large concentrations of negatively charged
  crystallines
• Positively charged cations enter the lens cell to maintain
  electrical neutrality
• pH- 6.9-7.2
• Aminoacids transported in lens via energy dependent carrier
  mechanisms
8/25/2012                                                      31
• Lipids-high concentration of cholesterol and sphingomyelin
         membrane rigidity
• Glutathione –major antioxidant in lens
                  synthesized by GSH in lens
                  present in reduced state
• Ascorbic acid-synthesized by cililary body into aqueous
                 antioxidant property
• Inositol- osmolyte
            membrane rigidity
• Taurine- osmolyte
            antioxidant

8/25/2012                                                32
Pump-leak mechanism




8/25/2012             33
Functions of lens

• Refraction
  Accounts for 35% of total refractive power of eye (15D out of total
   of 58D)
• Light transmission
   Focusing of visible light rays on the fovea
   Preventing, damaging- ultra-violet radiation, from reaching
   the retina
• Accomodation
• Organizer of anterior segment

8/25/2012                                                       34
REFRACTIVE PROPERTIES




8/25/2012               35
ACCOMODATION

• Lens has the capacity to change the focussing power
     of the eye for distant and near vision
• Accomodation can be divided into
        physical process- measure of change in shape of
                          lens
        physiological process- measure of ciliary muscle
                               contraction
• Near reflex-Contraction of ciliary muscles
                   Contraction of pupils
8/25/2012
                   Convergence of visual axis            36
8/25/2012   37
Theories of accomadation
1)Helmholtz theory-ciliary muscle contraction



                         relaxation of zonules



                               lens-spherical

• aging—lens rigid—difficulty to change shape
• Classical theory


8/25/2012                                        38
2) Schachar’s theory– ciliary muscle contraction



                        equatorial zonules tensed



                        shape changes in lens

Aging—diameter of lens grow—less space for proper functioning of
ciliary muscles

3) Coleman’s theory—
• Lens and zonules—diaphragm
• Shape altered by pressure difference b/w aqueous and vitreous
• Ciliary muscle-alters pressure gradient
8/25/2012                                                          39
Maintenance of transparency

•   Thin epithelium
•   Regular arrangement of lens fibers
•   Little cellular organelles
•   Little extracellular space
•   Orderly arrangement of lens proteins
•   Relative dehydration
•   Semipermeable character of lens capsule
•   Avascularity
•   Antioxidants
8/25/2012                                     40
LENTICULAR METABOLISM

• Continous supply of ATP required for-
1.     Transport of ions and aminoacids
2.     Maintanence of lens dehydration
3.     Continous protein synthesis
4.     GSH synthesis
• Major site – epithelium
• Source of nutrient supply-aqueous humour


     8/25/2012                               41
Glucose metabolism

• Energy production entirely dependent on glucose
  metabolism
• Glucose enters lens by simple diffusion and
  facilitated diffusion
• Epithelial cells- GLUT-1
• Lens fibre cells-GLUT-3
• Glucose is rapidly metabolized via glycolysis so that
  level of free glucose in lens < 1/10 level in aqueous


8/25/2012                                                 42
8/25/2012   43
1)Anaerobic metabolism
• Accounts for 85% of glucose metabolism by lens
• Provides > 70% of energy for lens
• 1 mole of glucose gives 2 moles of ATP
• Lactate generated undergoes 2 pathways of metabolism
• Further metabolism via Kreb’s cycle
• Diffusion from lens into aqueous

2)Aerobic metabolism (Krebs cycle)
• Limited to epithelium
• 1 mole of glucose gives 38 moles of ATP
• Only 3% of lens glucose metabolized by this pathway
• But generates up to 20% of total ATP needs of lens
8/25/2012                                                44
3)Hexose monophosphate shunt
• Accounts for 5% of glucose metabolism by lens
• Important source of NADPH required for other
  metabolic pathways e.g. sorbitol pathway and
  glutathione reductase
4)Sorbitol pathway
• Accounts for 5% of glucose metabolism by lens
• When sorbitol accumulates within cells of lens, it
  sets up an osmotic gradient that induces influx of
  water and lens swelling, and ultimate loss of lens
  transparency

8/25/2012                                              45
Changes during aging
1)Changes in structure
• Crystallins—proteolysis,decresed solubility,aggregation
               racemization and deamidation of aminoacids
• Cytoskeleton—proteolysis and insolubilization—disassembly
   of fibres
• Leads to opacities –nuclear sclerosis—senile cataract

2)Less elasticity of lens— loss of power of accomodation—
presbyopia

3)Overall reduction in light transmission
8/25/2012                                                     46
DISEASES OF LENS
1)CONGENITAL DISORDERS
• Coloboma
• Lenticonus
• Lentiglobus
• Microspherophalus
• Mittendorf dot

2)CATARACTS
• Congenital
• Acquired

8/25/2012                47
3) Miscellaneous disorders
• Posterior capsular opacification
• Aphakia
• Pseudophakia
• Exfoliation of capsule
• Psuedoexfoliation and psuedoexfoliation glaucoma
• Lens induced glaucoma
• Ectopia lentis
• Lens induced uveatits
• Loss of accomodation-aging,cataract,surgery

4)Several systemic diseases are also associated with disorders of
the lens
8/25/2012                                                       48
Lens

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Lens

  • 2. ANATOMY 1. Gross anatomy • Biconvex, transparent, crystalline structure • Ability to change shape • divides eye into anterior and posterior segments • 2 surfaces-anterior and posterior 8/25/2012 2
  • 3. ciliary body Zonules Lens Zonules ciliary body 8/25/2012 3
  • 6. DIMENSIONS OF LENS 10 mm 6 mm 8/25/2012 6
  • 8. A)Capsule • Acellular elastic structure • basement membrane -type 4 collagen+sulphated GAG • Variable thickness • Zonules run from ciliary processes and fuse onto outer layer of capsule • Main function is to mold the shape of the lens in response to tension from zonules 8/25/2012 8
  • 9. B)Anterior epithelium • Single layer of nucleated epithelial cells interconnected with gap junctions and desmosomes • The only metabolically active part of lens • Functionally divided into 2 zones- i] Pre-equatorial zone- columnar cells Actively dividing and differentiating into lens fibers ii]Central zone-cuboidal cells i) Transports solutes between lens and aqueous ii) Secretes capsular material • Maintains the osmotic balance of lens 8/25/2012 9
  • 10. C)Lens substance • Composed of lens fibres • Consist of primary and secondary fibers • Produced by mitosis of epithelial cells in the pre- equatorial zone • They elongate and undergo differentiation with pyknocytosis and eventual loss of cell oraganelles and nucleus • This is an important factor in the transparency of the lens 8/25/2012 10
  • 11. • As lens fibres elongate and new ones form, the older ones are pushed towards the depth of the lens • Lens bow-shifting of lens nuclei forms a visible line in the equator • Fibres are arranged in zones in which fibres growing from opposite directions meet in sutures • Consist of nucleus and cortex 8/25/2012 11
  • 13. 8/25/2012 13
  • 14. 8/25/2012 14
  • 15. Cortex • Youngest lens fibres • It is located peripherally, and is composed of secondary fibres formed continuously after puberty 8/25/2012 15
  • 16. Nucleus • Central part with oldest fibres • Dense and compactly arranged lens fibres • Higher refractive index than capsule • Different zones depending on period of development 8/25/2012 16
  • 18. 8/25/2012 18
  • 19. Anterior Suture posterior suture ( erect Y ) inverted Y 8/25/2012 19
  • 21. Zonules of zinn • Suspensory ligaments/ciliary zonules • Series of fibres from ciliary process • Holds the lens in position • Assist action of ciliary muscle • Attached to lens capsule at zonular lamella 8/25/2012 21
  • 22. Parts of ciliary zonules 8/25/2012 22
  • 25. EMBRYOLOGY 1)Formation of lens vesicle • 4 weeks • Optic vesicle induces lens placode from ectoderm • Lens placode invaginates and becomes lens pit • Optic vesicle also invaginates and becomes optic cup • Lens pit separates from ectoderm to become the lens vesicle 8/25/2012 25
  • 26. 8/25/2012 26
  • 27. 2)Formation of lens fibers and zonules • Primary lens fibres—fibres formed upto 3rd month Cells in posterior portion of lens vesicle elongate to fill vesicle forms emryonic nucleus • Secondary lens fibres—3rd month to entire life Cells in anterior portion of vesicle divide actively and elongate includes all other nucleus • Lens capsule-produced by anterior epithelial cells • Lens zonules—from neuroectoderm in ciliary area(3rd – 5th month) • Tunica vasculosa lentis--nourishment to embyonic lens branch of hyaloid artery disappears before birth 8/25/2012 27
  • 29. LENS PROTEINS Water soluble lens crystallins • 90% of total lens protein 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, 6 distinct subgroups 3) Gamma crystallin • Smallest crystallin • Least abundant-2% Water insoluble proteins • Insoluble albuminoids-12% 8/25/2012 29
  • 30. WATER • Lens –dehydrated state • Unique arrangement of proteins within lens fibres • Low protein osmotic activity within lens • Tightly packed fibres with minimum extracellular spaces • Lens epithelium transports water into the fibre mass • Half of the water -protein hydration • Water excreted via aquaporin in the equator into aqueous • Important factor maintaining lens transparency 8/25/2012 30
  • 31. Electrolytes • Active transport of ions and low molecular weight metabolite takes place between lens and aqueous humour • Epithelium contains Na-K-ATPase and a calmodulin- dependent Ca-activated ATPase for the active transport of electrolytes • Fibre cells contain large concentrations of negatively charged crystallines • Positively charged cations enter the lens cell to maintain electrical neutrality • pH- 6.9-7.2 • Aminoacids transported in lens via energy dependent carrier mechanisms 8/25/2012 31
  • 32. • Lipids-high concentration of cholesterol and sphingomyelin membrane rigidity • Glutathione –major antioxidant in lens synthesized by GSH in lens present in reduced state • Ascorbic acid-synthesized by cililary body into aqueous antioxidant property • Inositol- osmolyte membrane rigidity • Taurine- osmolyte antioxidant 8/25/2012 32
  • 34. Functions of lens • Refraction Accounts for 35% of total refractive power of eye (15D out of total of 58D) • Light transmission Focusing of visible light rays on the fovea Preventing, damaging- ultra-violet radiation, from reaching the retina • Accomodation • Organizer of anterior segment 8/25/2012 34
  • 36. ACCOMODATION • Lens has the capacity to change the focussing power of the eye for distant and near vision • Accomodation can be divided into physical process- measure of change in shape of lens physiological process- measure of ciliary muscle contraction • Near reflex-Contraction of ciliary muscles Contraction of pupils 8/25/2012 Convergence of visual axis 36
  • 37. 8/25/2012 37
  • 38. Theories of accomadation 1)Helmholtz theory-ciliary muscle contraction relaxation of zonules lens-spherical • aging—lens rigid—difficulty to change shape • Classical theory 8/25/2012 38
  • 39. 2) Schachar’s theory– ciliary muscle contraction equatorial zonules tensed shape changes in lens Aging—diameter of lens grow—less space for proper functioning of ciliary muscles 3) Coleman’s theory— • Lens and zonules—diaphragm • Shape altered by pressure difference b/w aqueous and vitreous • Ciliary muscle-alters pressure gradient 8/25/2012 39
  • 40. Maintenance of transparency • Thin epithelium • Regular arrangement of lens fibers • Little cellular organelles • Little extracellular space • Orderly arrangement of lens proteins • Relative dehydration • Semipermeable character of lens capsule • Avascularity • Antioxidants 8/25/2012 40
  • 41. LENTICULAR METABOLISM • Continous supply of ATP required for- 1. Transport of ions and aminoacids 2. Maintanence of lens dehydration 3. Continous protein synthesis 4. GSH synthesis • Major site – epithelium • Source of nutrient supply-aqueous humour 8/25/2012 41
  • 42. Glucose metabolism • Energy production entirely dependent on glucose metabolism • Glucose enters lens by simple diffusion and facilitated diffusion • Epithelial cells- GLUT-1 • Lens fibre cells-GLUT-3 • Glucose is rapidly metabolized via glycolysis so that level of free glucose in lens < 1/10 level in aqueous 8/25/2012 42
  • 43. 8/25/2012 43
  • 44. 1)Anaerobic metabolism • Accounts for 85% of glucose metabolism by lens • Provides > 70% of energy for lens • 1 mole of glucose gives 2 moles of ATP • Lactate generated undergoes 2 pathways of metabolism • Further metabolism via Kreb’s cycle • Diffusion from lens into aqueous 2)Aerobic metabolism (Krebs cycle) • Limited to epithelium • 1 mole of glucose gives 38 moles of ATP • Only 3% of lens glucose metabolized by this pathway • But generates up to 20% of total ATP needs of lens 8/25/2012 44
  • 45. 3)Hexose monophosphate shunt • Accounts for 5% of glucose metabolism by lens • Important source of NADPH required for other metabolic pathways e.g. sorbitol pathway and glutathione reductase 4)Sorbitol pathway • Accounts for 5% of glucose metabolism by lens • When sorbitol accumulates within cells of lens, it sets up an osmotic gradient that induces influx of water and lens swelling, and ultimate loss of lens transparency 8/25/2012 45
  • 46. Changes during aging 1)Changes in structure • Crystallins—proteolysis,decresed solubility,aggregation racemization and deamidation of aminoacids • Cytoskeleton—proteolysis and insolubilization—disassembly of fibres • Leads to opacities –nuclear sclerosis—senile cataract 2)Less elasticity of lens— loss of power of accomodation— presbyopia 3)Overall reduction in light transmission 8/25/2012 46
  • 47. DISEASES OF LENS 1)CONGENITAL DISORDERS • Coloboma • Lenticonus • Lentiglobus • Microspherophalus • Mittendorf dot 2)CATARACTS • Congenital • Acquired 8/25/2012 47
  • 48. 3) Miscellaneous disorders • Posterior capsular opacification • Aphakia • Pseudophakia • Exfoliation of capsule • Psuedoexfoliation and psuedoexfoliation glaucoma • Lens induced glaucoma • Ectopia lentis • Lens induced uveatits • Loss of accomodation-aging,cataract,surgery 4)Several systemic diseases are also associated with disorders of the lens 8/25/2012 48

Editor's Notes

  1. Anterior thickness greaterInverted basmnt membrane
  2. Thiker anteriorlyThiker in pre equatorial regions
  3. Fibre cell cycle stops-CDK INHIBITORS AND Rb geneElongation—microtubuleesFibredifferensiation—fibroblast gf and insulin likgfOrganelle degradation-15 lipoxygenase
  4. Adhesive junctions by microtubules—early stagesBall and socket junctions– on reaching the sutures—membrane intact during accomodation
  5. •Pars orbicularis –The part of the zonules which lie over pars plana.•Zonular plexus- part of the zonules that lie between the cilliary processes.•Zonular fork¬- the point of angulation of the zonule, which lies at the mid zone of cilliary valleys.•Zonular limbs- consists of◦Anterior zonular limb: passes from pars plana to preequatorial part of the lens.◦Posterior zonular limb: passes from pars plicata to postequatorial part of the lens.◦Equatorial Zonular limb: passes from pars pliacata to lens equator.Pars orbicularis –The part of the zonules which lie over pars plana.Zonular plexus- part of the zonules that lie between the cilliary processes.Zonular fork¬- the point of angulation of the zonule, which lies at the mid zone of cilliary valleys.Zonular limbs- consists ofAnterior zonular limb: passes from pars plana to preequatorial part of the lens.Posterior zonular limb: passes from pars plicata to postequatorial part of the lens.Equatorial Zonular limb: passes from pars pliacata to lens equator.
  6. Hyaloidzonules are the single layers of fibers which connect the anterior hyaloid of vitreous at the border of the patellar fossa to pars plana and pars plicata.
  7. Alpha-chaperone activity-heat shock protein-prevent protein aggregation and precipitationBeta gamma—buffering of calcium in lens fiber cell cytoplasm
  8. The composition enables the lens to have a refractive index considerably greater than its fluid environment and yet remain sufficiently hydrated to be deformable during the process of accommodation
  9. Ascorbic acid also is pro-oxidant
  10. Lens if not formed– absence of corneal endothelium abnormaldifferensiation of corneal stroma absence of iris,ciliarybody,anterior chamber
  11. CatarcatNuclera sclerosis
  12. Insoluble esp alpha crystallins—bind to hydrophobic domains of misfolded proteins