For residents and ophthalmologists

1. PHYSIOLOGY OF THE CORNEA
By Desta G.(MD,Optha R1)
Moderator Menen A. (MD, consultant
Ophthalmologist, corneal surgeon)

2. SEMINAR OUTLINE
• Introduction
• Embrology of the cornea
• Optical properties of cornea
• Metabolism of cornea
• Hydration of cornea
• Transparency of cornea
• Wound healing

3. Introduction
• It forms anterior 1/6th of the globe
• It is avascular, highly transparent
• It is principal optical media of
refraction=43D
• Protects intraocular structures of the eye
• It is thinner centrally than peripherally
• Has five layers

5. Dimensions and Topography
• Anterior: Elliptical
Diameter
Horizontal:11.7mm
Vertical:10.6mm
Radius curvature: 7.8mm
• Central thickness ranges 440-650um(0.53mm)
• Peripheral:700um(0.71mm)
• Surface area is about 1.3cm2
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• Posterior :circular
Diameter:11.7mm
Radius curvature;6.5mm

6. Embryology of cornea
• The separation of the lens vesicle from the surface
ectoderm initiates the development of the cornea
• With the separation of lens vesicle the surface
ectodermal cell proliferates to form epithelium of
cornea

7. Embryology cont.
• primate epithelium -acellularcorneal stroma, also
known as the Bowman's layer=20 wks of
gestation
• A first wave of neural crest-derived
mesodermal cell .—primitive endothelium (5th
wk)---descement membrane-- 8th week.

8. • second wave of mesoderm begins to grow
centrally from the limbus between the
epithelium and endothelium. ---cellular stroma
7wk
• At birth horizontal diameter is 9.8 mm
(surface area 102 mm2),
• 75% to 80% of adult

9. Optical properties
• The average index of refraction of the cornea
and tear film taken as a whole is about 1.376
• The refractive power for the anterior surface
of the cornea may be computed by the
following formula:
• D = n -n/r = D = 1.376-1.000/0.0078 =48.2′

10. Optical cont.
• The posterior surface of the cornea is bathed
with aqueous humor. By applying the same
formula, we
• arrive at the following value for the optical
power of the posterior corneal surface, where
n′ is the
refractive index of aqueous humor (1.336):
• D = n -n/r = 1.336-1.376/ 0.0065=-6.2′

11. • Therefore, the total optical power of the
cornea is 48.2 - 6.2, or approximately 42.0 D
• Because the cornea is thinner in the center
than in the periphery, it should act as a minus
lens but functions as a plus lens because the

12. aqueous humor neutralizes most of the minus
optical power on the posterior corneal surface.
If we compute the power of the posterior
corneal surface in air, we would find the
following:
•D=1.000-1.375/0.0065 =-96.0

13. Corneal physiology
• Primary concerned with
a.Source of energy of cornea that fuel the
corneas metabolic activity.
b. corneal transparency and its maintenance
c. Hydration status of the cornea
d.Wound healing mechanism

14. l. Corneal metabolism
• Metabolic stability depends on
a. Supply of oxygen
b.Supply of glucose
c. Supply of nutrients
Source of oxygen
l. Atmospheric oxygen dissolved in tear film=main
ll. From Aqueous humor
lll. Limbal capillaries

15. Metabolism of the epithelium
• Average temperature 34.8°c
• Main source of energy from glucose and
glycogen
• Glucose by diffusion from the aqouoes humor
and glycogen from epithelial store
• Glucose is metabolized in the corneal
epithelium primarily by anaerobic glycolysis
(Embden-Meyerhof pathway);

17. • however, up to 35% of glucose enters the
hexose monophosphate (HMP)shunt.
• The HMP shunt produces nicotinamide-
adenine dinucleotide phosphate (NADPH).
• Important for production of nucleic acid

18. • Glucose in the cornea may also enter the
sorbitol pathway, which produces sorbitol
and fructose.

19. • The cornea consumes approximately 3.5 μL
of oxygen/cm2/hour
• Under aerobic conditions, pyruvate from
glycolysis can enter the tricarboxylic acid
cycle (Krebs cycle),
• Less common because of low epithelial
mitochondoria

20. • Under hypoxic conditions (e.g., during contact
lens wear), pyruvate is converted to lactate
• Cant pass through the apical epithelial barrier
cells so it accumulates within the stroma.
• Maintains the PH between 7.3-7.4

21. • Associated with this lactic acid is anoxia of the
epithelial cells,.
• The acidification of the extracellular fluid may
interfere with
• cellular metabolism and mitosis, leading to
epithelial thinning and erosion.

22. • The cytochrome P450 system is also functional
in the corneal epithelium.
• Under conditions of hypoxia or inflammation,
• Arachidonic acid is metabolized to yield 12(R)-
hydroxyeicosa-tetraenoic acid (12(R)HETE)
and 12(R)-hydroxyei-cosatrienoic acid
(12(R)HETrE)

23. • has the potential to diffuse from the
epithelium to the endothelium and inhibit
Na+/K+ ATPase
• Ultimately resulting in corneal edema

24. • Corneal stroma is metabolically quisent.

25. Endothelial metabolism
• Atmospheric oxygen is the primary source of
oxygen to the endothelium.
• glycolysis accounts for 93% of the conversion of
glucose-6-phosphate to pyruvate in the
endothelium.
• The aerobic tricarboxylic acid cycle converts 30%
of the pyruvate to ATP,
• whereas the remaining 70% is converted to lactic
acid by the anaerobic pathway

26. Corneal hydration
• Water content of cornea 78% highest by
any connective tissue in the body
• It depends upon the mechanical and
functional integrity of its cell component
Impairment of this results corneal edema and
in loss of transparency

27. Factors affecting corneal hydration
Pump mechanism of corneal endothelium and the
enzymes
•Na/k ATPase pump system
•NA/H exchanger
•Carbonic anhydrase enzyme
•Bicarbonate dependent ATPase
Evaporation of water from corneal surface
Barrier function of epethelium and endothelium
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28. Hydration cont.
It can be summarized as
•Low-permeability barrier of the corneal
epithelium
•Water imbibing nature of corneal stroma
•High-permeability barrier: the corneal
endothelium

29. Low permeability nature
The epithelial cells are held together by
desmosomes, (zonula occludens ) tight
junctions at their peripheral intercellular
margins
•while the basal surface is attached to
Bowmans layer through
hemi desmosomes,
type VII collagen anchoring fibrils,
anchoring plaques

30. Zonula occludens tight junctions are
characterized by
fusion of the adjacent cell membranes
resulting in obliteration of the intercellular
space
•made up of the tight junction proteins ZO-1,
JAM-A, occludin,
and claudin-1, as well as some other claudin
subtypes.

32. This barrier prevents the movement of ions
and thus
•fluid from the tears into the stroma,
•reduces some evaporation,
•and protects the cornea from infectious
pathogens

33. • The most superficial squamous cells at the
external surface form a high-resistance
(8–16 kΩ·cm2) barrier to the external
environment

34. Hydration cont.
Water transport out of the cornea via
•1. aquaporins
•2. ion exchangers

35. Hydration cont.
Aquaporins
•are small integral membrane proteins
residing in the plasma membrane
•bidirectional
A. water selectives
B. glycerol selectives

36. • AQP1, AQP2, AQP4, AQP5, and AQP8 are
water selective
• AQP3, AQP7, and AQP9 transport glycerol
and perhaps other small solutes

37. Hydration cont.

38. Stroma.
•The stroma imbibes water because of the
large anionic proteoglycans Donan effect
•IP=IOP-SP
•Sp=55mmHg
•ensuring the hydrophilic environment in
the stroma responsible for maintaining the
regular spacing contributing to
transparency.

40. High-permeability barrier: the
corneal
endothelium
Endothelium
•The endothelial layer allows a slow leak of
fluids and solutes from the aqueous into
the cornea due to the “leaky” occluding
type of tight junction that joins them.

41. Low permeability cont…
The intercellular space is known to contain
apical hemi desmosomes (macula occludens)
tight junctions and lateral gap junctions
•thereby forming an incomplete barrier with
a preference to the diffusion of small
molecules

42. Macula occludens tight junctions are
•Characterized by partial obliteration
of the intercellular space and partial retention
of a 10-20 nm wide intercellular space
•low electrical resistance (25 Ω·cm2) barrier to
the aqueous humor flow

44. At birth,
• the central endothelial cell density (ECD) of
the cornea is around 5000 cells/mm2
•decline in central ECD with age that typically
involves two phases:
a rapid and a slow component

45. • ECD decreases exponentially to about 3500
cells/mm2 by age 5 and
• 3000 cells/mm2 by age 14–20
Thereafter,
• a slow component occurs where central
ECD decreases to a linear steady rate of
0.3–0.6 percent per year,
• around 2500 cells/mm2 in late adulthood

46. Leaky pump function
studies show
3 million Na+/K+-ATPase pump sites are
present in the basolateral membrane of a single
corneal endothelial cell
average pump site density of 4.4 trillion
sites/mm2

50. Corneal transparency
Cornea transmits nearly 85-99% of the light that enters it
which is achieved by several
1. MAURICE THEORY
‘the transparency of stroma is due to lattice type
arrangement of collagen fibrils with perfect dimensional
order’.
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53. 2.Theory of GOLDMAN
‘Cornea is transparent because the fibrils are small in
relation to light and don’t interfere with light
transmission unless they are larger than one half
length of light’
 destructive interference light scatter.

54. Ctn..
2.Corneal epithelium and tear film
• Epithelial non keratinization
• Regular and uniform arrangment of corneal
epithelium
• Junction between cells its compactness
3.Corneal avascularity
4.Non myelinated nerve fibers
5.Corneal hydration
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55. Wound healing
• Epithelial wound healing.
• limbal corneal epithelial stem cells produce
the progenitor cells.
Has three distinctive steps
1)cell migration,
2)cell proliferation,
3)and cell adhesion

56. 4- to 6-hour latent phase occurs where the
epithelium responds by
desquamating damaged cells,
polymerizing actin filaments,
Synthesizing structural proteins, and
releasing all hemidesmosomal attachments

57. 1,The migratory step
 independent of cell proliferation
flattened monolayer of epithelial cells slide
over the abraded areas and re-establish a
barrier
60 to 80 μm/hour
heals to normal thickness around 50 μm
approximately 1 to 4 weeks
hurricane keratopathy??

58. • What is conjuctival transdifferentiation??
• This basic knowledge of limbal syem cells has
helped to develop the concept autologes and
autograaft stem cell transplant

59. Stromal healing
• Usually heals by scaring
• The following steps are usually seen
apoptosis,
proliferation,
migration, and
possibly activation of keratocytes
along with causing stromal edema

60. corneal stromal injury is immediately followed
by
a zone of keratocyte apoptosis around the site
of stromal injury
influx of transient mixed acute and chronic
inflammatory cell infiltration
proliferation and migration of surviving
keratocytes

61. • Finally differentiation of the keratocytes into a
transiently metabolically activated cell type
called an activated keratocyte
• it synthesizes and deposits the extracellular
matrix of the stromal scar

62. Endothelium healing
• Following injury to the central endothelium,
both the central and peripheral cell densities
(cells/mm2) and percent hexagonal cells are
reduced,
• whereas the coefficient of variation of cell size
(an indicator of polymegathism) is increased

63. Steps…
• Stage 1 (0 to 3 days) is characterized by
an initial coverage of the wound by pleomorphic
spindle-shaped cells that form a functional but
incomplete barrier
• stage 2 (4 to 7 days), the cells assume a
flattened configuration, have an irregular
polygonal shape, and establish normal pump-
site density and barrier function

64. • Stage 3 (8 to 30 days) is characterized by a
continuation of the remodeling of the
monolayer

65. • Human corneal de compensation occurs when
the cell density drops below 500 cells/mm2

66. Other functions of the cornea
•Drug delivery
•Protection against UV light

67. References
• Duanes clinical ophtalmology 2012
• clinical anatomy and physiology of visual system
Remington’s 3rd edition
• ADELER’S physiology of the eye 11th
edition
• Online sources
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