BS - Cornea Structure and Metabolism Part 2 - Week 2

Question 1

Does corneal thickness vary in the population, or is it consistent?

Answer 1

Varies greatly.

Question 2

Is corneal thickness maintained throughout the day, or does it vary?

Answer 2

Varies throughout the day and with posture.

Question 3

What happens to corneal thickness if the endothelium is damaged?

Answer 3

Massive increase in corneal thickness.

Question 4

What happens to corneal thickness if the epithelium is damaged?

Answer 4

Swells, but less effect than endothelial damage.

Question 5

How is corneal transparency dependent on corneal hydration?

Answer 5

Hydration is highly regulated.
Stromal swelling pressure drives water across the epi- and endothelium.
Fluid pumps balance this water leak via ion and fluid transport at the endothelium.

Question 6

Describe the 5 steps that allow stromal water control by the epithelium.

Answer 6

1. Tight junctions is squamous epithelium are high resistance.
2. Na+K+ ATPase pumps on the basolateral cell membranes pump Na+ ions towards the stroma.
3. This reduces Donnan’s effect by lowering the negative charge, and provides Na+ gradient for Na/Cl cotransporter.
4. Cl- and Na+ ions move from stroma to cell via the Na/Cl cotransporter.
5. Cl- ions diffuse into tears creating an osmotic gradient drawing water out of the stroma.
   Na+ is recycled, driving Cl- to the tear film, drawing water out.

Question 7

How does the sympathetic nervous system affect corneal hydration?

Answer 7

Release of catecholamines such as noradrenaline can modulate the epithelial pathway.

Question 8

Describe the relative contributions of energy producing pathways that affect corneal hydration.

Answer 8

Anaerobic pathway predominates both epi- and endothelium

35-65% is via the pentose phosphate pathway.

Question 9

How much is the TCA cycle utilised in the epi- vs endothelium?

Answer 9

TCA cycle is less active in the epithelium vs endothelium

Question 10

From where do the majority of epithelial glucose originate from?

Answer 10

The aqueous, not the tear film.

Question 11

What happens to the epithelium pathway under hpoxic conditions?

Answer 11

Low 02 availability means high utilisation on anaerobic pathway, causing lactate buildup, and reduced tear film pH

Question 12

What is the typical origin of 02 related corneal swelling?

Answer 12

Epithelial in origin.

Question 13

What happens if corneal endothelium is lost?

Answer 13

They flatten out to account for the lost space, but lose hexagonal shape, and are much less effective.

Question 14

Are the tight junctions at the cell apex of the endothelium leaky or very tight?

Answer 14

Slightly leaky.

Question 15

There is a constant leak of water across the endothelium. What 2 factors contibute to this?

Answer 15

Intraocular pressure

Stromal gel pressure

Question 16

Does the endothelium pump water?

Answer 16

No.

Question 17

Describe the 10 steps to establish an endothelial osmotic gradient.

Answer 17

1. Basoateral Na+/2HCO3- cotransporter loads the cell with bicarbonate and chloride from the stroma.
2. Bicarbonate and chloride move to the aqueous humour via passive channels
3. Carbonic anhydrase converts excess bicarbonate to CO2.
4. CO2 diffuses into the aqueous humour and is converted to bicarbonate through membrane-bound CA-IV.
5. Basolateral Na+/K+/2Cl- cotransporter loads the cell with Cl-
6. Na+ pumped out by basolateral pumps using ATP
7. Na+ moves to the aqueous humour due to its relative negativity, diffueses between the cells.
8. Aquaporins allow water to move to the aqueous humour.

Question 18

Where does endothelial O2 originate from?

Answer 18

Mainly from the aqueous humour. Closed eyes has no effect, unlike epithelium.

Question 19

How long does it take for lost epithelium to regenerate?

Answer 19

Within 24-48h

Question 20

Name the 4 main stages of epithelial wound healing.

Answer 20

Latency
Migration
Proliferation
Attachment

Question 21

Describe what occurs during latency in epithelial wound healing. How long does it last?

Answer 21

Apoptosis, increased cell metabolism, structural re-organisation, fibronectin bandaid. Occurs within 1 hour.

Question 22

Describe what occurs during migration in epithelial wound healing.

Answer 22

Filopodia at the leading edge, causing a cellular avalanche

Question 23

Describe what happens during proliferation in epithelial wound healing.

Answer 23

Limbal cells divide rapidly, restoring cell density

Question 24

Describe what happens during attachment in epithelial wound healing.

Answer 24

Re-establishment of hemidesmosomes to anchoring filaments in BM, can take up to a year

Question 25

What do limbal stem cells produce during epithelial wound healing?

Answer 25

Transient amplifying cells, which proliferate quuickly, and migrate towards the centre.

Question 26

Does oedema occur during stromal healing? Why/why not?

Answer 26

Yes, due to injury and inflammatory cell infiltration.

Question 27

Why do myofibroblasts appear?

Answer 27

During heavy epithelial trauma, fibroblasts may convert to myofibroblasts, which contract and aid wound healing. May be problematic during surgical procedures.