Anatomy & Physiology of The Cornea

1. DEPT. OF OPTHALMOLOGY
SHER-E-BANGLA MEDICAL COLLEGE HOSPITAL,
BARISAL.
DR. MD. NURUL ISLAM
DO STUDENT
SESSION – JULY, 2013
23-12-2014
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2. The Cornea
The cornea is a transparent avascular tissue
with a 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
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3. Dimensions
Anterior surface:
- Elliptical, about 11.7 mm horizontally and
10.6 mm virtically
Posterior surface:
- Circular, about 11.7 mm in diameter
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4. Contd…
Thickness:
- Centrally about 0.52 mm
- Peripherally about 0.67 mm
Surface area:
- About 1.3 cm² (one-sixth of the
globe)
Optical zone:
- Cornea is almost a sphere, the
central 1/3rd is called optical zone
about 5.4 mm
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5. Contd…
Radius of curvature:
- Anterior surface – about 7.8 mm
- Post. Surface – about 6.5 mm
Refractive power: +43.1 D
(Air-tear = +43.6 D, Tear-cornea = +5.3 D, Cornea-aqueous = -5.8 D)
Refractive index: 1.376
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6. Contd…
Topography:
- Shape of cornea is important for fitting of contact
lenses
- Small spherical zone of ant. curvature (2-4 mm) is
decentered up & outwards with visual axis, but
correctly centered for pupillary aperture is
termed as corneal apex or cap
- Curvature varies from apex to limbus, greater
flattening in nasally and superiorly
- Cornea is flatter in men than in women
- Cornea flattens slightly on convergence
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7. 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 %
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8. Embryonic origin of Cornea:
The formation of cornea is induced by the
lens and the optic cup at the 7th weeks
ofintrauterine life.
• Corneal epithelium – Surface ectoderm
• Bowman’s membrane – Mesenchyme
• Stroma – Mesenchyme and Neural crest
• Descemet’s membrane – Synthesized by
endothelium
• Endothelium – Neural crest
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9. Structure
Behind the precorneal tear film there are five
layers of cornea:
1. Epithelium
2. Bowman’s layer
3. Stroma
4. Descemet’s membrane
5. Endothelium
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10. Epithelium:
The corneal epithelium is -
- Stratified, squamous and non-
keratinized
- Continuous with conjuctival
epithelium at limbus but having no
goblet cells
- 50-90 µm in thickness
- Consists of 5 or 6 layers of
nucleated cells resting on a basal
lamina, namely- a. Basal cells
b. Wing cells
c. Surface cells
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11. Basal cells:
- Deepest cell layer
- Stand in a palisade manner
on basal lamina
- Germinative layer of the
epithelium
- Columner with rounded
heads and flat bases
- Nucleus is oval and oriented
parallel to the cells long axis
Contd…
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12. Wing or umbrella cells:
- Second epithelial cell layer (1-2 layers of cells)
- Polyhedral cells
- Convex anteriorly forming cap over basal cells
and send processes between them
- Nucleus is oval and oriented parallel to corneal
surface
Contd…
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13. Surface cells:
- Most superficial 2-3 layers of
cells
- Also polyhedral and become
wider & flattened towards the
surface
- Flattened nuclei project
backwards leaving the surface
perfectly smooth
Contd…
- Most superficial cells are mostly hexagonal in shape
and exhibit surface microvilli or microplicae
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14. Ultrastructural features:
- Epithelial cells shows usual organelles like
other actively metabolizing cells
- Moderately abundant mitochondria in wings
& middle layer cells but small and scarce in
basal cells
- Wing & superficial cells have high glycogen
content
Contd…
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15. - Tonofibrils: cells contain a cytoplasmic
meshwork of electrondense intermidiate
filaments composed of cytokeratins
- The plasma membrane of contiguous cells
interdigitative to each other
- Adhesion is achieved by –
• Tight junctions & desmosomes – surface cells
• Desmosomes – wings & superficial cells
• Desmosomes & Hemidesmosomes – in basal cells
Contd…
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16. Contd…
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17. - In the basal cells there are anchoring
filaments which pass through the
hemidesmosomal structure to be inserted
into 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
Contd…
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18. Basal lamina:
- The basal lamina is secreted by the basal
cells
- 0.5 - 1 µm wide
- Ultrastructurally it is distinguished in to two
patrs –
i. Lamina lucida (superficial)
ii. Lamina densa (deep osmiophilc)
Contd…
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19. - The lamina consist of collagen and glycoprotein
constituents which integrated with Bowman’s
layer by array of short anchoring filaments
- Lipid solvent, stromal oedema and inflamation
may loosened the cohesion between Bowman’s
zone and lamina
- With old age, in diabetes and in some corneal
disorders it becomes thickened and
multilamellar
Contd…
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20. 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
Contd…
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21. - The XYZ hypothesis:
1. Thoft R. and Friend J. (1983) proposed on
the basis of experimental evidence that
both limbal basal and corneal basal cells
are the source for corneal epithelial cells,
and there is a balance among division,
migration & shedding.
Contd…
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22. The corneal epithelium is maintained by a balance
among sloughing (Z) of cells from the corneal surface,
cell division (X) in the basal layer and renewal of basal
cells by centripetal migration (Y) of new basal cells
originating from the limbal stem cells.
Contd…
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23. 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
Contd…
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24. 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
Contd…
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25. - In case of total epithelial loss including total
limbus, cornea is covered with vascularized
conjunctival type of epithelium by adjacent
conjunctiva
- If a small part of limbus with stem cell is
retained then conjunctival type of epithelium
is gradually disappear and metabolic behavior
of corneal epithelium re-established very
slowly
Contd…
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26. Bowman’s layer: (Ant. Limiting lamina)
- Modified region of anterior
stroma
- Acellular homogeneous zone
- 8 – 14 µm thick
- Ant. surface is smooth &
parallel with corneal surface
- It delineates the anterior
junction between cornea
and limbus
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27. Ultrastructural features:
- Ultrastructurally it is a felted meshwork of fine
collagen fibrils of uniform size in a ground
substance
- Posteriorly it becomes blended & interweaving
with fibrils of ant. stroma
- Compact arrangement of collagen gives it great
strength and relatively resistant to trauma both
mechanical and infective
Contd…
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28. - Convex ridges may generate
over surface if its tension is
relaxed during indentation,
hypotony or manipulation
causes ant.corneal mosaic,
polygonal or chicken-wire
pattern over surface
- No regeneration and replaced
by coarse scar tissue
- It is perforated many places by
nerve to epithelium
Contd…
Fig.: Ant.corneal mosaic
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29. 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
- Width about 9 – 260 µm
- Height about 1.15 – 2 µm
- Small population of cells – keratocytes
present
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30. - 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
Contd…
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31. Contd…
Fig.: Arrangement of stromal lamellae
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32. Ultrastructural features:
- Each lamellae comprises of a band of collgen
fibrils arranged in parallel with each other
- Fibrils show typical 64 nm periodicity of
connective tissue collgens with a microperiod
of 6 nm
- 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 lamellae
Contd…
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33. - The keratocytes occupy 2.5 – 5 % of total
stromal volume and is responsible for synthesis
and maintaining of collagen & proteoglycan
substance of stoma
- Keratocytes:
- Long, thin, flattened cells (maximally 2µm thick)
running parallel to corneal surface
- Having long flattened nuclei, sparse cytoplasm
but contains full component of organells
- Position – between the lamellae
Contd…
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34. - There stellate processes extened for great distance
and frequent contacts are made with other
keratocytes in same horizontal plane forming gap
junctions
- Lymphocytes, macrophages and
polymorphonuclear leucocytes (very rarely) also
found in stroma ocationally
Contd…
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35. Stromal repair:
- Repair of stroma after small injuries involves: -
Keratocytes activation
Migration & transformation into fibroblasts
Production of scar tissue
Initial fibrils are large & irregular
Contd…
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36. Remodelling of scar tissue occurs, it ensues –
1. Thinning of fibrils
2. Reformation of lamellae over months
3. Increase in tranperency
- Larger wounds provoke rapid vascular response
and leaving vascularised scar along with
lymphatic channels
Contd…
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37. 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 :- about 5 µm
at adult :- 10 – 12 µm
- There is a distinct structural difference
between fetal & postnatal components
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38. - It is a strong resistant sheet
- It thickens with age and in some corneal
degenerative conditions
- Major protein of DM is Type IV collagen
Contd…
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39. Ultrastructural features:
- In adult human, the anterior 1/3rd of DM
corresponds to fetal part, which is like a
laminated structure and shows an irregular
banded pattern in cross section
- In tangential section it appears to consist of
superimposed plates forming a lamellar pattern
Contd…
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40. - Posterior 2/3rd formed after birth and consist of a
homogeneous fibrogranular material
- The zone adjoining the endothelium is the most
recently formed
- Modified hemidesmosomes attachment present in
between DM & endothelium
Contd…
Descemet’s membrane
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41. Hassal-Henle warts:
- It is the peripheral excrescence produced by
focal overproduction of basal lamina like
material in aging cornea
- No clinical abnormality in corneal function
Descemet’s warts of central cornea is called
Cornea Guttata, it is associated with increased
permiability of endothelium
Contd…
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42. Contd…
Fig.: Cornea Guttata in Fuchs’ dystrophy
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43. Posterior embryotoxon:
• Schwalbe’s line may
hypertrophied in congenital
anomalies and appears as visible
shelf on gonioscopy, is called
posterior embryotoxon
Contd…
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
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44. 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
Contd…
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45. Endothelium:
- It is a single layer of
hexagonal, cuboidal cells
attached posterior
aspect of DM
- It is nuroectodermal in
origin
- Corneal endothelial cells
production is relatively
fixed, it is about 500000
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46. - Endothelial cells density –
- about 6000 cells/mm² at birth
- 26% lost in 1st year
- Further 26% lost over next 11
years
- Rate of cell loss slows and
stabilizes around middle age
and then it is about 2500
cells/mm²
- If cells density falls upto 500
cells/mm² corneal oedema
devlops and transparency
reduced
Contd…
Endothelium of a healthy cornea
Endothelium of a rigid contact
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47. - At birth cells are 10 µm
in height, with age it
becomes flattened to 3-
5 µm and 18-20 µm width
- Single oval nucleus located
centrally
- Cells shape is hexagonal in
youth with age it become
polymorphic
Contd…
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48. Ultrastructural features:
- The anterior cell membrane
(Basal) is attached with DM by
modified hemidesmosomes
- The posterior cell membrane
(Apical) facing Anterior
chamber shows 20-30
microvilli
- Lateral borders produce a
complex interdigitation with
neighboring cells
Contd…
Fig.: 3-D view of deep cornea
showing part of endothelium, DM,
Stroma
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49. - Cell junctions with surrounding cells at lateral
surfaces –
- Ant. 2/3rd – maculae adharentes
- Post. 1/3rd & apicolateral edges – macculae
occludentes
- 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
Contd…
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50. 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
Contd…
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51. Fluid regulation:
- The state of relative deturgescence of stroma
is maintained by this delicate monolayer of
cells by two ways –
- 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
Contd…
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52. 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
- Thus, after injury, the endothelial cell density
falls, the cell area increases and the cell height
decreases
Contd…
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53. Blood supply of Cornea:
- The cornea is an avascular
structure
- Small loops derived from
the anterior ciliary vessels
invade its periphery for
about 1 mm.
- Actually, these loops are
not in cornea but in the
subconjunctival tissue
which overlaps the cornea.
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54. Nerve supply of Cornea:
- Cornea is rich in sensory nerve supply derived
from ophthalmic division of trigeminal nerve via
anterior ciliary nerves and nerves to the
surrounding conjunctiva –
Ant.ciliary nerve enter the pericoroidal space a short distance behind the limbus
Connect with each other & conjunctival nerve and form pericorneal plexus
60-80 myelinated branches pass into cornea
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55. After 1-2 mm lose myelin sheaths and divide into anterior and posterior groups
Anterior nerves (40-50) pass through stroma and form plexus
subjacent to Bowman’s layer
Nerve fibres then penetrate Bowman’s layer and form subepithelial plexus
Fibres then divide dichotomously to form a parallel network
which run for upto 2 mm
Contd…
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56. And give rise to fine free nerve terminals to superficial epithelial layers
The posterior groups of nerves (40-50) pass posteriorly to
innervate the posterior stroma excluding Descemet’s membrane
Contd…
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57. Sentinel of the eye:
• The adrenergic fibres from cervical
sympathetic, supply the limbus also
supply almost whole of the eye and its
appendages, giving warning of injury for
instance by a foreign body, its called
‘sentinel of eye’
Contd…
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58. 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
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59. 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
Contd…
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60. - 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
Contd…
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61. Metabolic pathways:
- Three processes or pathways –
1. Penntose shunt (Hexose monophosphate
shunt) – occurs both In hypoxic and normoxic
condition
- Forms NADPH and Pentose (Ribose 5-P) from gulcose
which are used in nucleic acid synthesis
2. Glycolysis (Embden meyerhof pathway) –
anaerobic process, 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
Contd…
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62. Contd…
Fig.: Metabolism of Glucose in cornea
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63. 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
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64. ii) Goldman et al. (1968): He suggest, a perfect
crystalline lattice periodicity is not always necessary for
sufficient destructive interference. He explained, if fibril
separation and diameter is less than a third of the
wavelength of incident light, then almost perfect
transparency will ensue. This is the situation which
obtains in normal cornea.
Contd… A B
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65. 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
Contd…
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66. Factors affecting corneal Hydration:
i. Stromal swelling pressure exerted by GAGs
ii. Barrier function of epithelium and endothelium
iii. 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
iv. Evaporation of water from corneal surface
v. Intraocular pressure
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67. 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
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68. Corneal wound healing:
• Discussed earlier of this presentation with
every layers..
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