Cataract

Question 1

What is a Hypermature cataract?

Answer 1

A mature cataract ages and leaks water, causing shrinkage of the lens capsule

Question 2

What is a Morganian cataract?

Answer 2

Cortical lens matter liquifies with inferior displacement of the nucleus in the capsular bag

Question 3

What happens to oxidation in normal lens ageing compared with cataract formation?

Answer 3

Decreases (as opposed to cataract which has extensive oxidation of lens proteins)

Question 4

What happens to γ-Crystallins in normal lens ageing?

Answer 4

They are synthesized less

Question 5

What happens to B-Crystallins in normal lens ageing?

Answer 5

Increase

Question 6

Name 4 changes that happen in normal ageing of the lens

Answer 6

1. The level of oxidation is lower than age related cataract
2. There is constant post-translational modification of lens proteins throughout lift
3. γ-Crystallins are synthesised less
4. B-Crystallins increase

Question 7

What are the changes that take place in age-related cataract

Answer 7

1. There is a breakdown of antioxidant mechanisms in the lens - mainly reduced glutathione levels
2. Increased proteolysis
3. Water influx:
   - Caused by free radicals that downregulate Na/K ATPases in the lens epithelium
   - Free radicals formed with UV light is absorbed by lens tryptophan which is then converted to compounds that act as photosensitizers and cause free radical formation
4. Decreased function of MIP26 aquaporin molecule - leading to water influx
5. a-cystallins denature - causing reduced chaperone activitiy
   - They bind to unfolded proteins but lack the ability to refold Bγ-Crystallins
6. These changes lead to:
   - Increased insoluble proteins
   - Increased amino acid oxidation
   - Increased Chromophores
   - Los of aA-Crystallins and γS-Crystallins

Question 8

Is oxidation increased or decreased in age-related cataract?

Answer 8

Increased - due to breakdown of antioxidant mechanisms, primarily reduced glutathione levels

Question 9

What causes water influx in age-related cataract?

Answer 9

Free radicals down regulate Na/K ATPase in the lens epithelium (Free radicals formed with UV light is absorbed by lens tryptophan which is then converted to compounds that act as photosensitizers and cause free radical formation )

Decreased function of MIP26 aquaporin

Question 10

Describe the mechanisms of Diabetic cataract

Answer 10

• High glucose and galactose in aqueous causes increased lens intracellular glucose
• This overwhelms the anaerobic glycolysis pathway - preventing the normal inhibition of the polyol pathway by aldose reductase
• Causes Upregulation of the polyol pathway and accumulation of poluols (sorbitol) in cells
• Drags water into cells. MIP26 is then activated
• Causes reduced ATP and Gluthione - and therefore oxidative damage

Question 11

What are the cellular changes that take place in cataract formation (regardless of cause)?

Answer 11

• Loss of cellular organisation
• Formation of vacuoles in lens fibres
• Water accumulation in cells
• Disruption of lens crystallin organisation and formation of Lens protein aggregates
• Accumulation of protein aggregates and chromophores leading to colour change (yellow, red, black)

Question 12

Which drugs are associated with cataract formation?

Answer 12

• Corticosteroids
• Chlorpromazine
• Amiodarone
• Aspirin
• Topical glaucoma meds e.g. Pilocarpine

Question 13

Which systemic diseases are associated with cataract formation?

Answer 13

Diabetes
Atropic dermatitis
Wilson’s disease
Neurofibromatosis type 2
Myotonic dystrophy

Question 14

Which ocular diseases are associated with cataract formation?

Answer 14

• Uveitis
• Myopia
• Acute angle closure glaucoma
• Retinal dystrophy (retinitis pigmentosa)