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Physiology of
Cornea
Dr. Tukezban Huseynova
Eye – Dr. Tuti
Apical cells
Small light
cells (young
cells)
Dark cells
(mature cells)
Part 1
I. EPITHELIUM
Epithelium,
5-7 cells layers
Apical Cells,
3-4 cells layer
Wing cells,
1-3 cells layer
Basal cells,
1 cells layer
Apical cells
These cells finally degenerate and are
sloughed from the corneal surface
vThis process results
In turnover of the entire
Epithelium every
7 days
Basal cells
Wing cells
Apical cells
Small light
cells (young
cells)
Dark cells
(mature cells)
Wing cells
Basal cells
Major keratin pair
K3 & K12
Minor keratin pair
K14 & K5
! The basal cell are distinguished from
limbal stem cells by the expression
of major Keratin pair
Basement Membrane
vLamina Lucida (anteriorly, 23nm)
vLamina densa (apposed to Bawmen’s layer)
vReticular lamina (within to Bawmen’s layer)
Cell Adhesion in the Epithelium
Cell Adhesion in the Epithelium
Cell Adhesion in the Epithelium
Junctional complexes of the cornea
Gap junction Tight junction
Limbus
Limbal epithelium
0.5 – 1 mm
Basal layer
Nonkeratinized, stratified
squamous corneal cells
Lies in superficial corneal
epithelial layers
Terminal
differentiated cells
Lies in the suprabasal layers
Postmitotic cells
Transient amplifying cell
Migrate centrally within
cornea to occupy its basal
layer
64-kD keratin
expression
Stem cells
Devision or Defferentiation
Maintenance of the Corneal epithelium
Maintenance of the Corneal epithelium
Y Y
X
X + Y = Z
Z
X, Y, Z Hypothesis of corneal epithelial maintenance.
X - proliferation of basal cells
Y - centripetal movement of cells
Z - cell loss from the surface
Epithelium wound healing
Injury Latent Phase
Cell migration
Cell proliferation
Cell adhesion
3 steps of corneal healing
Epithelium wound healing
Transient Amplifying cells (TA)
Step 1: Cell migration
Epithelium wound healing
Step 2: Cell proliferation
Limbal Stem Cells
Migration
Proliferation
and movement
toward surface
Migration
Epithelium wound healing
Fonte: João Alfredo Kleiner DVM, MSc
Clinical Case
Patient: 11 y.o., female
Complaints: severe ocular
pain in the right eye
Diagnosis: superficial
traumatic ulcer
Treatment: topical antibiotics,
artificial tears
clockwise vortex (whorl pattern)
Epithelium wound healing
Hurrycane keratopathy
Epithelium wound healing
Step 3: Cell adhesion
Migratory epithelial cells
Basal Lamina
Adhesion plaqes
Clinical Manifestation of Abnormalities in
Epithelium structure
v Epithelial basement
membrane dystrophy
(dot changes)
v Epithelial basement
membrane dystrophy
(fingerprints changes)
The main corneal biochemical components
ü Fibronectin–integrin
system
Epithelial movement
The main corneal biochemical components
ü Fibronectin–integrin
system
Epithelial movement
ü Hyaluronan
The main corneal biochemical components
ü Fibronectin–integrin
system
Epithelial movement
ü Hyaluronan
ü Proteolytic enzymes
The main corneal biochemical components
ü Fibronectin–integrin
system
Epithelial movement
ü Hyaluronan
ü Proteolytic enzymes
Cytokines and growth factors
ü Epidermal growth factor
The main corneal biochemical components
ü Fibronectin–integrin
system
Epithelial movement
ü Hyaluronan
ü Proteolytic enzymes
Cytokines and growth factors
ü Epidermal growth factor
ü Transforming growth factor-β
The main corneal biochemical components
ü Fibronectin–integrin
system
Epithelial movement
ü Hyaluronan
ü Proteolytic enzymes
Cytokines and growth factors
ü Epidermal growth factor
ü Transforming growth factor-β
ü Basic fibroblast growth factor (bFGF)
The main corneal biochemical components
ü Fibronectin–integrin
system
Epithelial movement
ü Hyaluronan
ü Proteolytic enzymes
Cytokines and growth factors
ü Epidermal growth factor
ü Transforming growth factor-β
ü Basic fibroblast growth factor (bFGF)
ü Interleukins
Part 2
II. BOWMAN’S LAYER
Modified region of anterior stroma
Characteristics
Thickness is 8 – 14 μm
Acellular homogeneous zone
It lacks fibroblast therefore after injury it is unable to regenerate-
replaced by course scar tissue
Anterior surface of this layer is smooth
The collagen fibres in Bowman's layer are
synthesized and secreted by stromal
keratocytes
Prevents keratocytes metaplasia to fibroblast and scar formation
Anchoring site for epithelial cells to ensure stability
Function
Prevents stromal keratocytes from exposure to epithelial growth
factors
Tough acellular layer provide mechanical supports
E – Epithelium
S – Stromal Stromal collagen fibers
B – Bowman's layer
Bar = 2 μm
III. STROMA
Stromal Structure
Made up of 200 – 250 lamellas of collagen fibers
The lamellas formed of bundles of collagen fibers
They stretch from limbus to limbus
At the limbus they turn and run circumferentially forming an
annulus 1.5 to 2.0 mm wide around the cornea (which maintains
the curvature of the cornea)
This has profound implication for possible alterations of stromal structure
during refractive or cataract surgery that may lead to possible refractive errors
Stromal Structure
Proteoglycans
The extrafibrillar material sometimes called the Ground Substance of the
stroma, is largely made up of
CD/DS
Decorin (type IV)
is the only CD/DS proteoglycan in the cornea.
More abundant in the anterior cornea than
in the posterior.
KS
More abundant in the posterior stroma.
ü Lumican
ü Keratocan
ü Mimecan
v CD/DS - chondroitin sulfat/dermatan sulfat
v KS - keratan sulfat
Proteoglycans
Function
Confer hydrophilic properties of stroma
Maintains corneal transparency
Helps in regular spacing of collagen fibers to ensure transparency
Keratocytes
Cellular component of the corneal stroma
Turn over every 2 to 3 days
Synthesize collagen
The cells are activated when the stroma is damaged
Differentiate into fibroblast during wound healing
There is a gap junction between cells
Corneal Transparency and Stromal Function
Interwoven fibrous collagen
The regular arrangement of collagen
mechanical strength
transparency of this tissue
Fibers of regular diameter
Interfibrillar distance less than a Wavelength of light
Avascularity
Relative dehydration
Interactions between Proteogycans and Collagen in the Stroma
Granular Dystrophy
Interactions between Proteogycans and Collagen in the Stroma
Granular Dystrophy
Lattice Dystrophy
Interactions between Proteogycans and Collagen in the Stroma
Granular Dystrophy
Lattice Dystrophy
Macular type 1 Dystrophy
Stromal Wound healing
Part 3
IV. DESCEMET’S LAYER
A The anterior part 3mm
P The posterior part which is secreted
after birth
Thickness
Note! There is a distinct structural difference
between fetal & postnatal components
at birth: 3 – 4 µm
at childhood: about 5 µm
at adult: 10 – 12 µm
Hassal-Henle warts
Descemet’s membrane abnormalities
Hassal-Henle warts
Corneal Guttata
Descemet’s membrane abnormalities
Hassal-Henle warts
Corneal Guttata
Descemet’s membrane abnormalities
Posterior
Embryotoxon
Spreading endothelial cells
Descemet’s wound healing
Injury
Synthesis of fresh
basal lamina
V. ENDOTHELIUM
Endothelial Cell Dencity, ECD
At birth:
about 6000 cells/mm²
At adults:
about 2500 cells/mm²
Endothelial Cell Dencity, ECD
The "+" indicates a larger cell, the "-" indicates
a smaller cell, and the numbers indicate the
number of sides forming the cell
Ultrastructural features
3-D view of deep cornea
showing
part of endothelium, DM,
Stroma
Nutrition of Endothelium
Endothelium gets its nutrition & O₂ from aqueous
Essential nutrients (such as glucose & amino acids) pass across its
surface to supply the cellular needs of all the corneal layers
Fluid regulation of Endothelium
Providing a barrier function to the ingress of salt and metabolites
to the stroma
Actively reducing the osmotic pressure of stroma by metabolically
pumping the bicarbonate ions out of the stroma to aqueous
The state of relative clearence of stroma is maintained by this delicate
monolayer of cells by two ways
Endothelial Repair
Physical & chemical damage to endothelium results in loss of cells
Neighbor cells move over to fill the gap by sliding process and
enlargement of cells occur
Thus, after injury, the endothelial cell density falls, the cell area
increases and the cell height decreases
Thank you
Eye_dr_tuti
Eye_dr_tuti

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Physiology of Cornea

  • 1. Physiology of Cornea Dr. Tukezban Huseynova Eye – Dr. Tuti Apical cells Small light cells (young cells) Dark cells (mature cells)
  • 4. Epithelium, 5-7 cells layers Apical Cells, 3-4 cells layer Wing cells, 1-3 cells layer Basal cells, 1 cells layer
  • 5. Apical cells These cells finally degenerate and are sloughed from the corneal surface vThis process results In turnover of the entire Epithelium every 7 days Basal cells Wing cells
  • 6. Apical cells Small light cells (young cells) Dark cells (mature cells)
  • 8. Basal cells Major keratin pair K3 & K12 Minor keratin pair K14 & K5 ! The basal cell are distinguished from limbal stem cells by the expression of major Keratin pair
  • 9. Basement Membrane vLamina Lucida (anteriorly, 23nm) vLamina densa (apposed to Bawmen’s layer) vReticular lamina (within to Bawmen’s layer)
  • 10. Cell Adhesion in the Epithelium
  • 11. Cell Adhesion in the Epithelium
  • 12. Cell Adhesion in the Epithelium Junctional complexes of the cornea Gap junction Tight junction
  • 13. Limbus Limbal epithelium 0.5 – 1 mm Basal layer Nonkeratinized, stratified squamous corneal cells Lies in superficial corneal epithelial layers Terminal differentiated cells Lies in the suprabasal layers Postmitotic cells Transient amplifying cell Migrate centrally within cornea to occupy its basal layer 64-kD keratin expression Stem cells Devision or Defferentiation Maintenance of the Corneal epithelium
  • 14. Maintenance of the Corneal epithelium Y Y X X + Y = Z Z X, Y, Z Hypothesis of corneal epithelial maintenance. X - proliferation of basal cells Y - centripetal movement of cells Z - cell loss from the surface
  • 15. Epithelium wound healing Injury Latent Phase Cell migration Cell proliferation Cell adhesion 3 steps of corneal healing
  • 16. Epithelium wound healing Transient Amplifying cells (TA) Step 1: Cell migration
  • 17. Epithelium wound healing Step 2: Cell proliferation Limbal Stem Cells Migration Proliferation and movement toward surface Migration
  • 18. Epithelium wound healing Fonte: João Alfredo Kleiner DVM, MSc Clinical Case Patient: 11 y.o., female Complaints: severe ocular pain in the right eye Diagnosis: superficial traumatic ulcer Treatment: topical antibiotics, artificial tears clockwise vortex (whorl pattern)
  • 20. Epithelium wound healing Step 3: Cell adhesion Migratory epithelial cells Basal Lamina Adhesion plaqes
  • 21. Clinical Manifestation of Abnormalities in Epithelium structure v Epithelial basement membrane dystrophy (dot changes) v Epithelial basement membrane dystrophy (fingerprints changes)
  • 22. The main corneal biochemical components ü Fibronectin–integrin system Epithelial movement
  • 23. The main corneal biochemical components ü Fibronectin–integrin system Epithelial movement ü Hyaluronan
  • 24. The main corneal biochemical components ü Fibronectin–integrin system Epithelial movement ü Hyaluronan ü Proteolytic enzymes
  • 25. The main corneal biochemical components ü Fibronectin–integrin system Epithelial movement ü Hyaluronan ü Proteolytic enzymes Cytokines and growth factors ü Epidermal growth factor
  • 26. The main corneal biochemical components ü Fibronectin–integrin system Epithelial movement ü Hyaluronan ü Proteolytic enzymes Cytokines and growth factors ü Epidermal growth factor ü Transforming growth factor-β
  • 27. The main corneal biochemical components ü Fibronectin–integrin system Epithelial movement ü Hyaluronan ü Proteolytic enzymes Cytokines and growth factors ü Epidermal growth factor ü Transforming growth factor-β ü Basic fibroblast growth factor (bFGF)
  • 28. The main corneal biochemical components ü Fibronectin–integrin system Epithelial movement ü Hyaluronan ü Proteolytic enzymes Cytokines and growth factors ü Epidermal growth factor ü Transforming growth factor-β ü Basic fibroblast growth factor (bFGF) ü Interleukins
  • 31. Modified region of anterior stroma Characteristics Thickness is 8 – 14 μm Acellular homogeneous zone It lacks fibroblast therefore after injury it is unable to regenerate- replaced by course scar tissue Anterior surface of this layer is smooth The collagen fibres in Bowman's layer are synthesized and secreted by stromal keratocytes
  • 32. Prevents keratocytes metaplasia to fibroblast and scar formation Anchoring site for epithelial cells to ensure stability Function Prevents stromal keratocytes from exposure to epithelial growth factors Tough acellular layer provide mechanical supports E – Epithelium S – Stromal Stromal collagen fibers B – Bowman's layer Bar = 2 μm
  • 34. Stromal Structure Made up of 200 – 250 lamellas of collagen fibers The lamellas formed of bundles of collagen fibers They stretch from limbus to limbus At the limbus they turn and run circumferentially forming an annulus 1.5 to 2.0 mm wide around the cornea (which maintains the curvature of the cornea) This has profound implication for possible alterations of stromal structure during refractive or cataract surgery that may lead to possible refractive errors
  • 36. Proteoglycans The extrafibrillar material sometimes called the Ground Substance of the stroma, is largely made up of CD/DS Decorin (type IV) is the only CD/DS proteoglycan in the cornea. More abundant in the anterior cornea than in the posterior. KS More abundant in the posterior stroma. ü Lumican ü Keratocan ü Mimecan v CD/DS - chondroitin sulfat/dermatan sulfat v KS - keratan sulfat
  • 37. Proteoglycans Function Confer hydrophilic properties of stroma Maintains corneal transparency Helps in regular spacing of collagen fibers to ensure transparency
  • 38. Keratocytes Cellular component of the corneal stroma Turn over every 2 to 3 days Synthesize collagen The cells are activated when the stroma is damaged Differentiate into fibroblast during wound healing There is a gap junction between cells
  • 39. Corneal Transparency and Stromal Function Interwoven fibrous collagen The regular arrangement of collagen mechanical strength transparency of this tissue Fibers of regular diameter Interfibrillar distance less than a Wavelength of light Avascularity Relative dehydration
  • 40. Interactions between Proteogycans and Collagen in the Stroma Granular Dystrophy
  • 41. Interactions between Proteogycans and Collagen in the Stroma Granular Dystrophy Lattice Dystrophy
  • 42. Interactions between Proteogycans and Collagen in the Stroma Granular Dystrophy Lattice Dystrophy Macular type 1 Dystrophy
  • 46. A The anterior part 3mm P The posterior part which is secreted after birth Thickness Note! There is a distinct structural difference between fetal & postnatal components at birth: 3 – 4 µm at childhood: about 5 µm at adult: 10 – 12 µm
  • 49. Hassal-Henle warts Corneal Guttata Descemet’s membrane abnormalities Posterior Embryotoxon
  • 50. Spreading endothelial cells Descemet’s wound healing Injury Synthesis of fresh basal lamina
  • 52.
  • 53. Endothelial Cell Dencity, ECD At birth: about 6000 cells/mm² At adults: about 2500 cells/mm²
  • 54. Endothelial Cell Dencity, ECD The "+" indicates a larger cell, the "-" indicates a smaller cell, and the numbers indicate the number of sides forming the cell
  • 55. Ultrastructural features 3-D view of deep cornea showing part of endothelium, DM, Stroma
  • 56. Nutrition of Endothelium Endothelium gets its nutrition & O₂ from aqueous Essential nutrients (such as glucose & amino acids) pass across its surface to supply the cellular needs of all the corneal layers
  • 57. Fluid regulation of Endothelium Providing a barrier function to the ingress of salt and metabolites to the stroma Actively reducing the osmotic pressure of stroma by metabolically pumping the bicarbonate ions out of the stroma to aqueous The state of relative clearence of stroma is maintained by this delicate monolayer of cells by two ways
  • 58. Endothelial Repair Physical & chemical damage to endothelium results in loss of cells Neighbor cells move over to fill the gap by sliding process and enlargement of cells occur Thus, after injury, the endothelial cell density falls, the cell area increases and the cell height decreases