L44 The Outer Coat: Sclera & Cornea PART 2

Question 1

What are the corneal requirements for optimal function?

Answer 1

• A source of oxygen
• A source of glucose
• A source of essential amino acids, vitamins, and minerals
• Elimination of waste products of metabolism

Question 2

As the cornea does not have its own blood supply what is it dependent on?

Answer 2

Adjacent structures for its metabolic requirements.

Question 3

How does the oxygen tension (basically amount of oxygen present) on the anterior surface of the cornea (front of the cornea) differ to that of the aqueous humour (which is on the other side of the cornea)?

Answer 3

When the eyes are open the oxygen
tension at the anterior corneal surface is equivalent to that of the atmosphere (155mmHg at sea level).

Whereas, estimates of oxygen tension in the
aqueous humour lie in the range of 20-80mmHg.

Question 4

When we cut off oxygen supply to the cornea (which we basically do when we close our eyes) what happens?

Answer 4

(Very little oxygen that could diffuse through the thickness of the eyelids).

There is a modification of the conjunctiva where at that particular region (basically underside of the eyelid) it is very vascular. This is where oxygen supply to the cornea comes from whilst our eyes are closed.

“The palpebral conjunctiva posseses a rich blood supply. Vessels lie in close proximity to the (corneal) epithelium. Furthermore, during eye closure oxygen tension at the corneal surface is equal to that of the palpebral conjunctiva”.

Question 5

How much oxygen does the cornea need?

Answer 5

Oxygen concentrations of at least 10% are required to avoid oedema(swelling) (this causes a loss of transparency).
Reduced oxygen availability is associated with measurable and observable changes in corneal function.
(Large inter-subject availability in oxygen requirements exist).

Question 6

How does corneal thickness vary throughout the day?

Answer 6

The cornea is approximately 5% thinner during waking hours than during sleep. (This is thought to be the result of overnight swelling during sleeping hours returning back to normal)

Question 7

Why does the cornea experince overnight swelling?

Answer 7

Overnight oedema may be the result of reduced oxygen availability or the result of changes in tear tonicity due to reduced tear evaporation.

“When eyes open in the morning tears evaporate , creating a slight tear hypertonicity (relatively higher concentration of salt) and subsequently corneal dehydration.”

Reasoning behind [WHEN WE ARE TALKING ABOUT TEARS -THINK TEARFILM]

When eyes are closed osmolarity of the tears is gonna be slightly higher than during the day. As eyes open concentration of salt becomes relatively lower. As soon as we open our eyes a proportion of tears evaporate - so we lose water and retain salt thus concentration of salt is going to slightly rise relative to the level of water. Osmolarity (basically concentration) of tears (think tearfilm) increases in the first hours of waking.- this is thought to draw water out of the cornea. As water moves from high to low gradient.

Question 8

What is osmolarity?

Answer 8

A measure of solute concentration.Higher osmolality means more particles in your serum. Lower osmolality means they’re more diluted

Question 9

What is tonicity?

Answer 9

The ability of an extracellular solution to make water move into or out of a cell by osmosis is know as its tonicity.

Question 10

How does the cornea meet its glucose requirement- is this from the tears?

Answer 10

The glucose concentration of the tears is low and insufficient to meet corneal needs.

Intracellular glucose reserves (in the form of glycogen in the corneal epithelium) serve as a glucose source during periods of metabolic stress.

The bulk of the glucose required by the
cornea is derived from the aqueous (which also acts as a source of
amino acids, vitamins and other metabolites)

It is likely that the limbal vascular
arcades provide oxygen and
nutrients to the peripheral cornea only

Question 11

How does the cornea meet its glucose requirement- is this from the tears?

Answer 11

The glucose concentration of the tears is low and insufficient to meet corneal needs.

Intracellular glucose reserves (in the form of glycogen in the corneal epithelium) serve as a glucose source during periods of metabolic stress.

The bulk of the glucose required by the
cornea is derived from the aqueous (which also acts as a source of
amino acids, vitamins and other metabolites)

It is likely that the limbal vascular
arcades provide oxygen and
nutrients to the peripheral cornea only

Question 12

What are the three principal pathways for glucose metabolism in the cornea?

Answer 12

Anaerobic glycolysis (produces lactic acid)

Hexose Monophosphate Shunt (Pentose Phosphate Pathway)

Aerobic Glycolysis (and Krebs Cycle)

Question 13

What is interesting about glucose metabolism of the corneal epithelium and stroma?

Answer 13

That despite the availability of glucose and oxygen , aerobic respiration does not occur as much as you would think since corneal epithelium cells dont have lots of mitochondria nor is much of it present in the stroma!

Question 14

In which part of the cornea is aerobic respiration predominantly happening?

Answer 14

Corneal endothelium - this has high number of mitochondria.

Question 15

How much incident light does the cornea transmit?

Answer 15

> 90% (over 90%) of incident light is transmitted by the cornea.

Question 16

Why is the cornea transparent if collagen fibrils potentially act as scatter sources?

Answer 16

1. Collagen fibrils are incredibly small (and regularly arranged-space between neighbours had to be equal)- the smaller they are the less light scatter.
2. Scattered light is eliminated by a process of destructive interference.

Question 17

Why is the state of corneal hydration an important determinant of corneal transparency?

Answer 17

Physiological hydration is maintained at 78% (cornea is 78% water). Transparency is maintained at + or - 5% of this value.

Question 18

What are hydrophilic properties of the cornea determined by?

Answer 18

Largely by Stromal proteoglucans and monovalent cations (e.g. chloride).

Question 19

What is a proteoglycan?

Answer 19

Proteoglycans are proteins that are heavily glycosylated via the addition of covalently bonded glycosaminoglycan chains (which are repeating disaccharide units).

Question 20

What is special about glycosaminoglycan chains of proteoglycans?

Answer 20

They are very hydrophilic - attract water.

Question 21

How many types of proteoglycans are present in the stroma and what are they?

Answer 21

Three main proteoglycans (but technically four).
Three main proteoglycans are:
Lumican 
Keratan 
Mimican. 

Fourth one is Decoran.

Question 22

As well as ensuring a hydrated cornea what else do Corneal proteoglycans ensure and how?

Answer 22

Transparency - studies on mice have shown that Lumican mutations develop opacification showing that lumican is essential for transparency.

Question 23

What is the function of decoran?

Answer 23

The function of decoran is unclear

Question 24

True or false - there are factors at play to stop the cornea being more than 78% hydrated.

Answer 24

True - the proteoglycans have a natural tendency to attract water and could technically keep going thus to stop this the cornea is kept in a state of relative dehydration.

Question 25

What is the mechanism for taking out excess water attracted by the proteoglycans (in order to keep the cornea around 78% hydrated as it physiologcally allows for best transparency)?

Answer 25

Pump-leak hypothesis

Question 26

What is the pump leak hypothesis and what does it relate to?

Answer 26

Both surfaces of the cornea, the epithelium and endothelium operate as barriers to stop water getting in, from the tearfilm and aqueous humour respectively. (side note- having tight junctions in both surfaces also helps with this).

Endothelium has a pumping mechanism that is able to take pout excess water. (We call this the endpothelial pump).

Question 27

What does the pump leak hypothesis refer to?

Answer 27

The cornea’s ability to rid itself of excess water.

Both surfaces of the cornea, the epithelium and endothelium operate as barriers to stop water getting in, from the tearfilm and aqueous humour respectively. (side note- having tight junctions in both surfaces also helps with this but cannot completely stop this).

Stromal swelling pressure is the driving force for water to ‘leak’ across the epithelial ans endothelial barrier layers.

This leak however is counterbalanced by pump mechanisms which reside in the epithelium and endothelium.

The endothelium accounts for at least 90% of the pumping activity of the cornea. Thus we refer to the ‘endothelial pump’ as significant in maintaining corneal transparency.

Question 28

What does the ‘endothelial pump’ in the pump leak hypotheisis do to get rid of excess water?

Answer 28

It pumps ions from the stromal side into the aqueous side , establishing an osmotic gradient for water to move out from the cornea into the aqueous humour.

Question 29

What is the major ion/substrate for the endothelial pump?

Answer 29

Bicarbonate ions

Question 30

In what direction does the cornea swell?

Answer 30

Cornea swells in an anterior-posterior direction (aka horizontally).

Question 31

How can corneal oedema be caused?

Answer 31

• Retardation of carbon dioxide efflux
• Stromal lactate accumulation
• Breach of epithelial or endothelial barriers
• Inhibition of ion pumps

Question 32

Why is an influx of water in the cornea bad ( as well as obviously corneal oedema)?

Answer 32

Influx of water increases the seperation between collagen fibrils causing increased light scatter.

Question 33

What is the regenration of the epithelium dependent on?

Answer 33

The integrity of the limbus.

A proportion of limbal cells act as stem cells and are ultimately responsible for corneal epithelial replacement.

Question 34

What are the palisades of Vogt?

Answer 34

The limbus contains radially-oriented fibrovascular ridges known as the palisades of Vogt that may harbour a stem cell population.

Question 35

How does the cornea ‘regenerate’ itself?

Answer 35

Stem cells divide and migrate into the cornea . The basal cells then become wing cells which then become squamous cells and then eventually we lose them into the tearfilm (desquamation).

It takes about seven days to completely replace corneal epithelium.