Fighting the cataract epidemic. Lecture 5 Flashcards
With regards to the internal circulation system what is observed with a diabetic cataract?
Osmotic damage is observed in diabetic cataracts
How can GSH levels change with cataracts?
A drop in GSH levels is observed in age related nuclear cataract
What defines a cataract?
Opacification of the lens severe enough to impair vision
Whats the prevalence of cataract blindness in 1st and 3rd world countries?
Underdeveloped countries = >50%
Developed countries = <5%
(of all blindness)
What increases the risk of cataract?
- Sunlight
- Severe diahorrea
- Diabetes
- Smoking
- Corticosteroids
- Genetic predisposition
- Poor nutrition
However biggest risk is simply old age.
What are we facing as the population ages?
A cataract epidemic
How are cataracts characterised?
By the region of the lens they affect
What are the types of cataract?
Cortical Cataract
Nuclear Cataract
What are the distinctions of the cortical cataract?
Seen as wedges or spokes in the outer cortex
Do cortical cataracts impair vision?
Rarely do they affect vision as this part of the lens is typically covered during the day by the iris.
In what region of the lens do cortical cataracts typically start?
Typically start in the inferior nasal lens (most exposed to the sunlight)
What causes a cortical cataract?
Generally associated with structural changes to fibres and biochemical changes too.
Describe cortical cataract histology:
- 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.
The swelling of fibre cells in cortical and diabetic cataract suggests the cataract has what component?
A osmotic component.
Failure of the osmotic regulatory systems.
What is the failure of osmotic regulatory systems due to?
- Na/K-ATPase inactivation
- increased membrane leakiness
- increased osmolality due to accumulation of sorbitol in diabetes (however unlikely as not much sortibol is produced)
What does the failure of osmosis regulation lead to?
- localised water accumulation
- cell swelling, membrane damage
- water clefts and refractive index fluctuations that cause opacities
What is related to the onset of nuclear cataract?
Age
What is associated with nuclear cataract formation?
Myopic shift in refraction initially
What may a nuclear cataract be characterised by?
Brunescence - opacification due to biochemical changes rather than fibre morphology.
Whats the histology of a nuclear cataract?
Compaction of some fibres in the nucleus otherwise no change.
What is the mechanism for age related nuclear cataract formation?
Oxidative damage to lens proteins
What causes oxidative damage to lens proteins?
Absorption of light by substances within the lens (eg. tryptophan) produces reactive oxygen species (ROS)
What are some examples of ROS?
Superoxide, O2 Hydrogen peroxide (H2O2) Hydroxyl radical (OH•)
What normally protects proteins from oxidative damage?
Oxidants are normally scavenged by antioxidants.
So why do nuclear cataracts form with age?
AS we age antioxidant mechanisms become depleted leading to oxidative damage.
What do increased levels of ROS cause?
• 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)
What does damage from ROS lead to?
These changes impact on the ability of the lens to control its homeostasis and therefore transparency resulting
in cataract
So why does only the nuclear lens form a cataract with age if antioxidant mechanisms become depleted?
This suggests that its a failure of the internal circulation system to deliver antioxidants to the nuclear core thus protecting the outer cortex.
Does blocking the lens circulatory system impair transparency?
No it does not.
Inhibiting the circulatory system affects what?
Transport of solutes and metabolites to the lens nucleus the outer cortex appears fine.
