BS - Metabolic Eye Diseases - Week 4

Question 1

True or false

The eye is not the most metabolically active of all tissue.

Answer 1

False, it is the most metabolically active

Question 2

Describe the three types of diabetes, and their onset.

Answer 2

Type 1 - little or no insulin produced, <18 years of age onset
Type 2 - resistance to insulin, >40 years of age onset
Gestational diabetes mellitus - during pregnancy

Question 3

What is the risk of blindness in those with diabetes?

Answer 3

25x

Question 4

Name 5 ophthalmic complications of diabetic retinopathy.

Answer 4

Corneal abnormalities
Glaucoma
Iris neovascularisation
Cataracts
Neuropathies

Question 5

What is the prevalence of diabetic retinopathy?

Answer 5

28.5% among those with diabetes >40.

Question 6

What percentage of blindness does diabetic retinopathy account for?

Answer 6

10%

Question 7

What is the main problem behind diabetic retinopathy?

Answer 7

Hyperglycaemia

Question 8

What does hyperglycaemia promote?

Answer 8

Insulin secretion, promoting glucose uptake by muscle and adipose

Question 9

What happens to the capillaries in diabetic retinopathy (3)?

Answer 9

Pericyte loss
Increased vascular permeability
Progressive vascular occlusion

Question 10

What happens to the capillary basement membrane in diabetic retinopathy?

Answer 10

Becomes thicker

Question 11

What are 5 metabolic consequences of hyperglycaemia?

Answer 11

Increased production of advanced glycation end products
Increased flux through the polyol pathway
Protein kinase C activation
Increased hexosamine pathway
These collectively increase oxidative stress

Question 12

What is a consequence of increased polyol pathway activity in hyperglycaemia?

Answer 12

NADPH is oxidised to NADP+, needed for glutathione, and also increases sorbitol

Question 13

What is a consequence of increased sorbitol?

Answer 13

Glycates nitrogen on proteins

Question 14

Can sorbitol cross cell membranes, and what is a consequence of this?

Answer 14

Cannot, and therefore accumulates. It produces oxidative stress on cells by drawing water into the insulin-independent tissue.

Question 15

What effect does aldose reductase inhibitor have (4)?

Answer 15

Protects against neuropathy, and can be used to treat hyperglycaemia.
Reduces sorbitol levels, and increases nerve fibre density.

Question 16

How do glycation end-products damage cells (3)?

Answer 16

Modification of intracellular proteins
Diffuse out of cells and modify ECM molecules
Diffuse out of cells and modify circulating proteins in blood such as albumin

Question 17

What can be used to prevent accumulation of glycation end-products?

Answer 17

Aminoguanidines

Question 18

PKC activation results in what four consequences?

Answer 18

Increased vascular permeability
Fibrosis (increased risk of vascular occlusion)
Bloodflow/autoregulation abnormalities
Increased pro-inflammatory factors

Question 19

What effect does hyperglycaemia have on PKC and how?

Answer 19

It increases the synthesis of diacylglycerol, activating protein kinase C

Question 20

Describe an experimental setup to confirm PKC association with hyperglycaemia (4).

Answer 20

Mice made diabetic using streptozotocin.
Fluorescein angiography not confined to blood vessels indicating leakage.
Small interfering RNA used to silence PKC.
Fluorescein leakage stopped.

Question 21

What is produced by the hexosamine pathway?

Answer 21

Amino acid precursors for proteoglycans, glycolipids, and glycoproteins.

Question 22

Does hyperglycaemia increase or decrease hexosamine pathway activity, and what does this result in?

Answer 22

Increases activity, resulting in too many N-acetylglucosaminne donated, leading to altered genes and proteins.

Question 23

What effect does hyperglycaemia have on GAPDH? What is it like in the retina?

Answer 23

Decreases activity

Activity in the retina is decreased only of glycaemic control is poor, otherwise normal.

Question 24

What is the common link between all four pathways and hyperglycaemia?

Answer 24

Increased oxidative stress inhibits glycolysis and pushes substrates upstream into alternate pathways.