ANATOMY AND PHYSIOLOGY OF CORNEA

1. ANATOMY AND PHYSIOLOGY
OF CORNEA
DR.K.V.SUDHEER

3. The word cornea has come from “Kerato”. The term “Kerato” in greek means
horn or shield like. Ancient Greek used to believe that cornea is derived from
same material like that of thinly sliced horn of animal.

4. THE CORNEA
 The cornea is a transparent avascular tissue with smooth,
convex outer surface and concave inner surface, which
resembles a small watch-glass.
 To meet the diverse functional demands the cornea must be:
- Transparent
- Refract light
- Contain the intraocular pressure
- Provide a protective interface

5. DIMENSIONS
 Microcornea:when HCD is less than 10mm
 Macrocorneawhen HCD is more than 13 mm

6. Shape :
- Prolate
Surface area:
- About 1.3 cm² (one-sixth of the globe)

7.  Radius of curvature:
- Anterior surface – about 7.8
mm
- Post. Surface – about 6.5
mm
 Refractive power: +43.1 D
 Refractive index: 1.376

8. COMPOSITION OF HUMAN CORNEA
 Water: 78 %
 Collagen: 15 %
of which: Type-I : 50-55 %
Type-III : 1 %
Type-IV : 8-10 %
Type-VI : 25-30 %
 Other protein: 5 %
 Keratan sulphate: 0.7 %
 Condroitin/dermatan sulphate: 0.3 %
 Hyaluronic acid: +
 Salts: 1 %

9. EMBRYONIC ORIGIN OF CORNEA:
Structure Derived from
Corneal
epithelium
Surface ectoderm
Stroma,
Descmet’s
membrane,
endothelium
Paraxial
mesoderm

10. STRUCTURE

11. EPITHELIUM:
 Stratified, squamous
and nonkeratinized
 Three types of cells are
seen
a.Superficial cells
b.Wing cells
c.Basal cells

12.  Basal cells:
- Germinative layer of the
epithelium
-only epithelial layer with
mitotic activity
 Superficial cells
- microvilli +
-helps in glycocalyx formation
and stability of tear fim.

13. - Adhesion is achieved by –
desmosomes And hemidesmosomes
- Desmosomes are tight junctions between cells
- Hemidesmosomes are tight junctions between cell and
basal lamina
- - Langerhans cells (cells of immune recognition system)
present near periphery. They are almost absent at central
cornea but aggregate in response to infection

14.  Epithelial Turnover:
- Early studies suggested that the epithelium replaced
approximately weekly by division of basal cells and the oldest shed
from the surface
- It is now recognized that the germinative region lies at the limbus,
the stem cells, and cells migrate at a very slower rate (123
µm/week) to the center of the cornea which may be as long as a
year

15.  - The XYZ hypothesis:
1. Thoft R. and Friend J. (1983) proposed that
both limbal basal and corneal basal cells are the
source for corneal epithelial cells, and there is a
balance among division, migration & shedding.

17.  Epithelial Repair:
Repair of corneal epithelial injury like abration follows a
distinctive sequence of events.
Injury (abration)
Cells at wound edge retract, thicken and lose attachment.
Travel in an amoeboid movement to cover the defect
Cells at wound edge ruffle and send out filopodia and
lamellipodia towards the center of wound

18. Migration process is halted by contact inhibition
They then anchor and
Mitosis resumes to re-establish epithelial thickness
Surface tight junctions re-establised
Adhesion with Bowman’s layer within 7 days (if basal
lamina intact)
 The healing process occurs rapidly, rate of cell
migration is 60 – 80 µm/hr

19.  Bowman’s layer: (Ant. Limiting lamina)
- Modified region of anterior stroma
- Acellular homogeneous zone
- 8 – 14 µm thick
- It delineates the anterior junction between cornea and limbus
 Compact arrangement of collagen gives it great
strength and relatively resistant to trauma both
mechanical and infective.

20. STROMA: (SUBSTANTIA PROPRIA)
 Stroma: (Substantia propria)
- About 500 µm thick (about 90% of
corneal thickness)
- Consists of regularly arranged
lamellae of collagen bundles, lie in
proteoglycan ground substance
with –
- 200 – 300 bundles – centrally
- 500 bundles – peripherally
- Small population of cells –
keratocytes present

21.  - Arrangement of lamellae –
- Lamellae are arranged in layers, parallel with each other &
with corneal surface
- In deeper stroma the lamellae form strap-like ribbons which
run approximately at right angles to those in consecutive
layers
- At the periphery this right-angular arrangement is slightly
changed where it gets scleral fibres
- At the limbus the bundles appeared to take a circular course

22. Fig.: Arrangement of stromal lamellae

23.  Ultrastructural features:
- Each lamellae comprises of a band of collgen
fibrils arranged in parallel with each other
- There is a unique uniformity of fibril diameter,
it is 22 (±1) nm from ant. to post.
- There is remarkable regularity of seperation
both within and between lamella

24. - The keratocytes occupy 2.5 – 5 % of total
stromal volume and is responsible for synthesis
and maintaining of collagen & proteoglycan
substance of stroma.
- There are stellate processes extened for great distance
and frequent contacts are made with other keratocytes in
same horizontal plane forming gap junctions

25.  Stromal repair:
- Repair of stroma after small injuries involves: -
Keratocytes activation
Migration & transformation into fibroblasts
Production of scar tissue
Initial fibrils are large & irregular

26.  Remodelling of scar tissue occurs, it ensues –
1. Thinning of fibrils
2. Reformation of lamellae over months
3. Increase in transparency
- Larger wounds provoke rapid vascular response
and leaving vascularised scar .

27. DESCEMET’S MEMBRANE: (POST. LIMITING
LAYER)
 - It is the basal lamina of corneal endothelium
- First appears at 2nd month of gestation and synthesis continue
throughout adult life
Thickness –
 at birth :- 3 – 4 µm
 at childhood :- about5µm
 at adult :- 10 – 12 µm

28. - It is a strong resistant sheet
- It thickens with age and in some corneal
degenerative conditions
- Major protein of DM is Type IV collagen

29.  Hassal-Henle bodies:
- It is the peripheral posterior excrescence produced by
focal overproduction of basal lamina like material in aging
cornea
- No clinical abnormality in corneal function

30. Schwalbe’s line:
• The peripheral rim of DM is the internal landmark of
corneal limbus and also it is the anterior limit of drainage
angle, is called Schwalbe’ line
Posterior embryotoxon:
Schwalbe’s line may hypertrophied in
congenital anomalies and appears as
visible shelf on gonioscopy, is called
posterior embryotoxon

31.  Repair of Descemet’s layer:
After traumatic interuption of DM (Path./Mech.)
Endothelium spread its cells to resurface the defect
Synthesis of fresh basal lamina
which is structurally identical to normal descemet’s layer

32.  Endothelium:
- It is a single layer of
hexagonal, cuboidal cells
attached posterior aspect of
DM
- It is mesenchymal in origin
- Corneal endothelial cells
production is relatively
fixed, it is about 500000

33. Endothelial cells density
- If cells density falls below 500 cells/mm² corneal oedema devlops
and transparency reduced

34. Endothelium is rich in subcellular organeles –
- large number of mitochondria, both rough and smooth endoplasmic
reticulum, free ribozomes, these reflects that endothelium is extremely
active metabolically
Nutrition to 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

35.  Endothelial Repair:
- Physical & chemical damage to endothelium
results in loss of cells
- Neighboring cells move over to fill the gap by
sliding process and enlargement of cells occur
(polymegathism)
- Thus, after injury, the endothelial cell density
falls, the cell area increases and the cell height
decreases

36. LIMBAL STEM CELLS:
 Only 5% to 15% of the cells in the limbus are stem cells
 The basal cells of limbal epithelium comprises the limbal
stem cells.
 They are the precursor for all other cells of the tissue
 They have a self maintaining population
 They accounts for only a small portion of total cells of
the tissue
 In vivo,they show slow cycling,but when placed in cell
culture,they demonstrate high potential to proliferate.
 They can not be differentiated with rest of the cells of
tissue.

37. BLOOD SUPPLY TO CORNEA:
 In normal condition, cornea does not contain any blood
vessels
 Anterior ciliary artery, a branch ophthalmic artery
forms a vascular arcade in the limbal region and
helps in corneal metabolism and wound repair by
providing nourishment.
 Absence of blood vessel in cornea is one of the
contributing factors for its transparency.

38. NERVE SUPPLY OF CORNEA:
 Density of the nerve ending in cornea is about 300
times of that of skin.
 The ophthalmic division of the trigeminal nerve has
three parts: the frontal nerve, the lacrimal nerve,
and the nasociliary nerve.
 The nasociliary nerve provides sensory innervation
to cornea.

42. CORNEAL NUTRITION & METABOLISM
 Cornea requires energy for normal metabolic
activities as well as for maintaining
transparency and dehydration
 Energy is generated by the breakdown of
glucose in the form of ATP
 Most actively metabolizing layers are
epithelium & endothelium

43.  Sources of Nutrients:
- Oxygen – mainly from atmosphere through
tear film, with minor amounts supplied by the
aqueous and limbal vasculature
- Normal Po₂ in tears is 155 mm Hg
- In aqueous is about 40 mm Hg
- Minimum 25 mm Hg Po₂ is needed for
maintaining deturgescent state and
transparency

44. - Glucose, amino acid, vitamins, and other
nutrients supplied to cornea by aqueous
humor, a lesser amounts from tears or limbal
vessels.
- Glucose also derived from glycogen stores in
corneal epithelium.
- Epithelium consumes O₂ 10 times faster than
stroma.

45. METABOLIC PATHWAYS:
 Three processes or pathways –
1. Pentose shunt (Hexose monophosphate
shunt) – occurs both In hypoxic and normoxic condition
forms NADPH and Pentose (Ribose 5-P) from glucose
which are used in nucleic acid synthesis
2. Glycolysis (Embden meyerhof pathway) –
Glucose/glycogen converted to pyruvate yelding 2 ATPs
3. TCA or Krebs or citric acid cycle – in aerobic
conditions pyruvate is oxidized to yield 36 ATP,
water, CO₂.

46. CORNEAL TRANSPARENCY
The cornea transmits nearly 100% of the light
that enters it. Transparency achieved by –
1. Arrangement of stromal lamellae
Two theories –
i) Maurice (1957): The transparency of the stroma
is due to the lattice arrangement of collagen fibrils.
He explained, because of their small diameter and
regularity of separation, back scattered light would
be almost completely suppressed by destructive
interference

47. ii) Goldman et al. (1968): Proposed that lattice
arrangement is not a necessary factor for for
stromal transparency . Cornea is transparent
because fibrils are small in relation to light and do
not interfere with light transmission unless they are
larger than one half of a wavelenght of light(2000
A).
 Both theories failed to explain why there is corneal
clouding occurs with raised IOP and why there is
corneal clearing occurs on reduction of IOP.

49. Other factors of corneal transparency –
2. Corneal epithelium & tear film
• Epithelial non-keratinization
• Regular & uniform arrangement of corneal epithelium
• Junctions between cells & its compactness and also
tear film maintain a homogenicity of its refractive index
3. Relative deturgescence state of normal cornea.
4. Corneal avascularity
5. Non myelenated nerve fibres

50. FACTORS AFFECTING CORNEAL HYDRATION:
i. Stromal swelling pressure exerted by GAGs
IP = IOP – SP or IP = 17 -60 = -43
i. Barrier function of epithelium and endothelium
ii. Hydration controled by active pump mechanisms of
the corneal endothelium
The enzyme pump systems are –
• Na⁺/K⁺ ATPase pump system
• Bicarbnate dependent ATPase
• Carbonic anhydrase enzyme
• Na⁺/H⁺ pump
i. Evaporation of water from corneal surface
ii. Intraocular pressure

51. DRUG PERMEABILITY ACROSS THE CORNEA
 Factors affecting drug penetration through the
cornea are –
1. Lipid and water solubility of the drug
2. Molecular size, weight and concentration of
drug
3. Ionic form of the drug
4. pH of the solution
5. Tonicity of the solution
6. Surface active agents
7. Pro-drug form

52. 1. LIPID AND WATER SOLUBILITY OF THE DRUG
 Drug should be amphipathic,should have both lipid
and wter soluble properties.
 Epithelium – lipophilic
 Stroma - hydrophilic

53. 2. MOLECULAR SIZE, WEIGHT AND
CONCENTRATION OF THE DRUG
 lipid soluble molecules can cross the corneal
epithelium irrespective of their molecular size,while
water molecules with size less than 4A only canfilter
through pores in cell membrane.
 Substances with molecular weight less than 100
can pass &more than 500 can not.

54. 3. IONIC FORM OF THE DRUG
 Capacity to exist in both ionic and non-ionic
forms,becaus only non-ionised drugs can penetrate
epithelium and ionised drugs can pass through
stroma.
 Florescein dye test

55. 4. PH OF THE SOLUTION
 Normal range – 4 to 10
 Any solution outside this range increases
permeability.

56. 5. TONICITY OF THE SOLUTION
 Hypotonic solutions increase permeability.
 Those below 0.9%NaCl.

57. 6. SURFACE ACTIVE AGENTS
 Agents which reduce surface tension,increase
corneal wetting and ,therefore ,present more drug
for absorption.
Eg.Benzalkonium chloride

58. 7. PRO-DRUG FORM
 Pro-drug forms are lipophilic which after absorption
through epithelium converted into proper drug
which can easily pass through stroma.
 Eg. dipivefrine - epinephrine

59. THANK YOU