Fighting the cataract epidemic. Lecture 5

Question 1

With regards to the internal circulation system what is observed with a diabetic cataract?

Answer 1

Osmotic damage is observed in diabetic cataracts

Question 2

How can GSH levels change with cataracts?

Answer 2

A drop in GSH levels is observed in age related nuclear cataract

Question 3

What defines a cataract?

Answer 3

Opacification of the lens severe enough to impair vision

Question 4

Whats the prevalence of cataract blindness in 1st and 3rd world countries?

Answer 4

Underdeveloped countries = >50%
Developed countries = <5%

(of all blindness)

Question 5

What increases the risk of cataract?

Answer 5

• Sunlight
• Severe diahorrea
• Diabetes
• Smoking
• Corticosteroids
• Genetic predisposition
• Poor nutrition

However biggest risk is simply old age.

Question 6

What are we facing as the population ages?

Answer 6

A cataract epidemic

Question 7

How are cataracts characterised?

Answer 7

By the region of the lens they affect

Question 8

What are the types of cataract?

Answer 8

Cortical Cataract

Nuclear Cataract

Question 9

What are the distinctions of the cortical cataract?

Answer 9

Seen as wedges or spokes in the outer cortex

Question 10

Do cortical cataracts impair vision?

Answer 10

Rarely do they affect vision as this part of the lens is typically covered during the day by the iris.

Question 11

In what region of the lens do cortical cataracts typically start?

Answer 11

Typically start in the inferior nasal lens (most exposed to the sunlight)

Question 12

What causes a cortical cataract?

Answer 12

Generally associated with structural changes to fibres and biochemical changes too.

Question 13

Describe cortical cataract histology:

Answer 13

• Start location is a point of fibre cell swelling and stolen fibre cells.
• This progresses to the formation of morgagnion globules and ultimately liquefaction of the cortex.

Question 14

The swelling of fibre cells in cortical and diabetic cataract suggests the cataract has what component?

Answer 14

A osmotic component.

Failure of the osmotic regulatory systems.

Question 15

What is the failure of osmotic regulatory systems due to?

Answer 15

• Na/K-ATPase inactivation
• increased membrane leakiness
• increased osmolality due to accumulation of sorbitol in diabetes (however unlikely as not much sortibol is produced)

Question 16

What does the failure of osmosis regulation lead to?

Answer 16

• localised water accumulation
• cell swelling, membrane damage
• water clefts and refractive index fluctuations that cause opacities

Question 17

What is related to the onset of nuclear cataract?

Answer 17

Age

Question 18

What is associated with nuclear cataract formation?

Answer 18

Myopic shift in refraction initially

Question 19

What may a nuclear cataract be characterised by?

Answer 19

Brunescence - opacification due to biochemical changes rather than fibre morphology.

Question 20

Whats the histology of a nuclear cataract?

Answer 20

Compaction of some fibres in the nucleus otherwise no change.

Question 21

What is the mechanism for age related nuclear cataract formation?

Answer 21

Oxidative damage to lens proteins

Question 22

What causes oxidative damage to lens proteins?

Answer 22

Absorption of light by substances within the lens (eg. tryptophan) produces reactive oxygen species (ROS)

Question 23

What are some examples of ROS?

Answer 23

Superoxide, O2
Hydrogen peroxide (H2O2)
Hydroxyl radical (OH•)

Question 24

What normally protects proteins from oxidative damage?

Answer 24

Oxidants are normally scavenged by antioxidants.

Question 25

So why do nuclear cataracts form with age?

Answer 25

AS we age antioxidant mechanisms become depleted leading to oxidative damage.

Question 26

What do increased levels of ROS cause?

Answer 26

• Cross-linking of membrane lipids & proteins • Damage to DNA • Cross-linking of proteins (disulphide bonds) causing crystallin aggregation & loss of solubility • Inactivation of enzymes (eg. glutathione)

Question 27

What does damage from ROS lead to?

Answer 27

These changes impact on the ability of the lens to control its homeostasis and therefore transparency resulting in cataract

Question 28

So why does only the nuclear lens form a cataract with age if antioxidant mechanisms become depleted?

Answer 28

This suggests that its a failure of the internal circulation system to deliver antioxidants to the nuclear core thus protecting the outer cortex.

Question 29

Does blocking the lens circulatory system impair transparency?

Answer 29

No it does not.

Question 30

Inhibiting the circulatory system affects what?

Answer 30

Transport of solutes and metabolites to the lens nucleus the outer cortex appears fine.