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MEDSCI 316 > Lecture 3 > Flashcards

Lecture 3 Flashcards

Molecular physiology of transparency - The cornea

1
Q

What is made of the same molecules as the sclera?

A

The cornea

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2
Q

What is the cornea a barrier between?

A

The outside environment and the insie of the eye

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3
Q

What makes the cornea a smooth optical surface?

A

Its interactions with the mucin tear layer?

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4
Q

What is the structure of the cornea?

A

3 cell layers: - 1) The epithelium layer which sits on the bowman’s membrane - 2) The stroma (substantia propria, SP) (90%) of the cornea - 3) Endothelium which sits on Descemet’s membrane (DM)

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5
Q

What is the structure of the corneal epithelium?

A

Stratified, non-keratinised squamous epithelium, 5 to 7 cells thick. 3 distinct layers: - 1) Basal cell layer - 2) Intermediate or wing cell layer - 3) Superficial cells

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6
Q

What do the 3 epithelial cell layers represent?

A

Different stages of epithelial cell terminal differentiation

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7
Q

Structure of basal cell layer?

A
  • Single layer of cuboidal cells sitting on Bowman’s membrane - Capable of cell division into wing cells
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8
Q

Structure of Wing Cell layers?

A
  • 1 to 3 layers of cells in intermediate stage of differentiation - Give rise to superficial cells
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9
Q

Structure of Superficial cell layer?

A

Terminally differentiated squamous cells that are sloughed off into tears

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10
Q

Function of corneal epithelium?

A
  • Barrier to invasion of eye by pathogens - Secretes fluid into tear film that contributes to removal of fluid from the stroma
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11
Q

How does corneal epithelium form barrier?

A

Via high resistance tight junctions between superficial cells. Damage to epithelium induces rapid wounding response

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12
Q

How is corneal epithelium maintained?

A

Process of differentiation means that epithelium is turned over every 7 days.

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13
Q

Corneal thickness is maintained by a balance between?

A
  • Cell loss form the surface (Z) - Proliferation of Basal cells (X) - Centripetal migration of stem cells from the limbus (Y)
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14
Q

What is the X+Y = Z hypothesis?

A

Proliferation + Migration = Cell loss equals a maintenance of integrity of corneal epithelium

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15
Q

What happens when the cornea is wounded?

A

It affects 3 cell layers differently. Can be accidental or intentional. Exposes the rest of corneal tissues and potentially the whole eye to infection.

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16
Q

Structure of the Corneal stroma?

A

-90% of cornea’s thickness - consists of water, ECM, collagen fibrils, keratocytes

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17
Q

What is the Corneal Stroma ECM made of?

A

Various proteoglycans

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18
Q

What are the Corneal Stroma collagen fibrils made of?

A

Primarily Type I collagen with lesser amounts of Type V and VI

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19
Q

Which collagen is required to initate assembly of which collagen into fibrils in the Corneal Stroma?

A

Type V for Type I

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20
Q

What are Keratocytes and their function?

A
  • Long, thin stellate cells which run parallel to the corneal surface - They secrete collagens and the ECM
21
Q

What does collagen give the cornea?

A

Its strength, elasticity, and shape

22
Q

How many collagen bundles are in the Corneal Stroma and what are their dimensions?

A

200 to 250, 2 microns thick, 9-260 microns wide.

23
Q

Diameter of collagen fibrils in Corneal Stroma and spacing?

A

30nm, spaced 42 to 44nm apart?

24
Q

What is uniform spacing of fibrils in the Corneal Stroma for?

A

Contributes to corneal transparency

25
Q

What is association between PGs and collagen fibrils?

A

PGs form ladder-like attachment along collagen fibrils and between them (hold bundles together)

26
Q

What are PGs made of?

A

A core protein and one or more covalently attached glycosaminoglycan (GAG) side chains. They are highly electrically charged

27
Q

What do PG core proteins maintain and modulate?

A

Initial diameter of the fibril.

28
Q

4 examples of PG core proteins?

A

decorin, lumican, keratocan, and biglycan

29
Q

3 types of GAG side chains?

A
  • Chondroitin sulfate/Dermatan sulfate (CD/DS-PG) - Keratan Sulphate (KS-PG) - Heparan Sulphate (HS)
30
Q

What determines spacing of collagen fibrils?

A

Small uniform size of PGs and Hydration properties of Keratan sulphate side chains

31
Q

Function of the stroma?

A
  • Stroma scatters less than 10% of incident light - Transparency is consequence of arrangement of individual collagen fibrils - Lattice structure is thought to act as diffraction grating allowing light scattering by individual fibrils to be cancelled by destructive interference
32
Q

Destructive interference model and what is thought to be important now?

A

Requires all collagen fibrils to be of equal size, which does not happen. Now is thought that what is important is local order (200nm) of fibrils which is uniform enough to account for transparency

33
Q

What does distance between fibrils need to be to maintain transparency?

A

Half (or less) the wavelength of light

34
Q

Describe the condition that can be caused by the high PG content in the ECM of the cornea.

A

Corneal Edema occurs as PGs are highly charged and attract ions into the stroma which then attract water, causing the stroma to swell (high colloid osmotic pressure). Swelling disrupts spacing of collagen fibrils and produces light scattering

35
Q

What counterracts the swelling of the Corneal stroma?

A

Active transport of ions by the epithelium and endothelium.

36
Q

What is the structure of the Corneal endothelium?

A
  • Single layer of hexagonal cuboidal cells attached to Descemet’s membrane - Functions to maintain stroma hydration - contains high density of mitochondria
37
Q

Describe the role of the endothelium

A
  • Majority of fluid removed from stroma by endothelium - Water FOLLOWS ions - Active outward-directed transport transport of HCO3- and NA+ drive fluid secretion that balances the passive ion and water leakage into the stroma driven by the colloid osmotic pressure imposed by the ECM
38
Q

What acts as the source of HCO3- in active transport at corneal endothelium?

A

Carbonic anhydrase

39
Q

Carbonic anhydrase equation?

A

CO2 + H20 <=> H2CO3 <=> H+ + HCO3-

40
Q

What transport is driven by the active transport of the corneal endothelium?

A

Solutes from the corneal stroma to the aqueous humour, eg Sodium

41
Q

What does the process of maintaining stroma hydration (and hence corneal transparency) require?

A

Energy and Oxygen

42
Q

Where does the cornea obtain nutrients?

A
  • The aqueous humour - Tears - small amount of diffusion from limbal vessels
43
Q

What nutrients does the cornea obtain from the aqueous humour?

A
  • Glucose - amino acids - vitamins
44
Q

What nutrients does the cornea obtain from tears?

A

Some glucose (10X less than aqueous) BUT all of oxygen necessary for aerobic metabolism

45
Q

What are the corneal epithelium and stroma dependent on for nutrients?

A

Diffusion of nutrients from the aqueous humour

46
Q

What is the corneal endothelium dependent on for nutrients?

A

Diffusion of O2 from tears, even though it is in direct contact with the aqueous humour

47
Q

What does a lack of nutrients or O2 in the cornea cause?

A

Reduced energy supply to endothelial pumps, inhibited fluid transport, stromal swelling, loss of corneal transparency.

48
Q

Describe Corneal Oxygen tension profiles

A
  • O2 levels in tears change through cornea due to lid closure and contact lens
  • Endothelium has highest need for aerobic metabolism and obtains O2 through tears
  • endothelium can tolerate reduction of tear O2 to below 55mHg, but soft contact lenses are signinficant barrier to corneal O2 supply
49
Q
A

MEDSCI 316 (4 decks)

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