BS - Bleaching and Recycling - Week 10

Question 1

What are RPE cells and where are they located?

Answer 1

Monolayer of pigmented cells located between choricapillaris and photoreceptors

Question 2

Name 6 functions of RPE cells.

Answer 2

• Absorption of light, heat
• Transport of nutrients, waste (glucose, omega 3, retinal, lactic acid)
• BRB
• Phagocytosis of shed OS (outer segment)
• Interacts with BM - for barrier function and selective transport
• Involved in photopigment recycling (interacting with photoreceptors)

Question 3

How many photoreceptors does each RPE cell form a functional unit with?

Answer 3

Around 23 photoreceptors

Question 4

What are the 2 components of photopigments, and where are they synthesised?

Answer 4

Opsin and chromophore

Question 5

Consider the components of a photopigment. What is the origin of each?

Answer 5

Chromophore - not made in the body, is derived from the diet.
Opsin - synthesised in the inner segment

Question 6

What are the 2 isomeric forms of retinal? And what causes them to change to the other?

Answer 6

11-cis and all-trans - converts to all-trans in response to light
All-trans is a straighter molecule

Question 7

What are some source of vitamin A?

Answer 7

B-carotene and vitamin A precursors from diet

Red/yellow vegetables, fish, dairy, eggs

Question 8

What is a retinoid?

Answer 8

Any derivative of vitamin A.

Question 9

What are the three active forms of vitamin A?

Answer 9

Retinal, retinol, and retinoic acid.

Question 10

In what form is vitamin A stored?

Answer 10

Retinyl ester.

Question 11

What two forms of retinoids can be readily interconverted?

Answer 11

Retinal and retinol.

Question 12

Where are retinyl esters typically found (2)?

Answer 12

Rich in the liver, also found in circulating chylomicrons

Question 13

What are retinyl esters complexed with in the bloodstream?

Answer 13

Transthyretin

Question 14

What happens if you eat a polar bear liver?

Answer 14

Le khod

Question 15

What happens to beta-carotene when eaten, and how? What does it form?

Answer 15

It is solubilised by bile salts and lipolytic enzymes into retinol.

Question 16

When beta-carotene is eaten, how is it transported out of the intestines?

Answer 16

Once converted to retinol, it binds to cellular retinol binding protein, CRBP, and is transported out.

Question 17

What form of retinoid can be found in chylomicrons? Where do these eventually end up, and are they a major source of retinoid for this structure?

Answer 17

Retinyl esters are incorporated into chylomicrons.

They can bind to the RPE, but is a minor source.

Question 18

In what 3 forms are retinoids stored in the liver?

Answer 18

Chylomicrons
Retinyl esters
Retinol palmitate

Question 19

Is vitamin A susceptible to oxidation or reduction?

Answer 19

Oxidation

Question 20

When not in retinyl ester form, what are retinoids always bound to?

Answer 20

Retinoid binding protein RBP

Question 21

How do retinoids avoid being filtered by the kidneys?

Answer 21

Retinoids and RBP complex with transthyretin

Question 22

Where do retinol-transthyretin complexes end up?

Answer 22

They bind to retinoid binding protein receptors on the RPE.

Question 23

What are the two sources of retinoids for the RPE, and which is major/minor?

Answer 23

Major - retinol-transthyretin complex binding to receptors on the RPE.
Minor - retinyl esters in chylomicrons reaching the RPE through the bloodstream.

Question 24

In what form is vitamin A within the RPE?

Answer 24

Retinyl ester.

Question 25

Can the retina function without vitamin A?

Answer 25

Yes

Question 26

What can vitamin A deficiency lead to (2)?

Answer 26

Night blindness

Dry eye

Question 27

What happens to the chromophore after it photoisomerises to all-trans retinal?

Answer 27

It separates from the opsin for recycling.

Question 28

What happens to all-trans retinal after it detaches from the opsin?

Answer 28

Is reduced to all-trans retinol via all-trans retinol dehydrogenase, requiring NADPH

Question 29

What happens to tROL?

Answer 29

Converted to transROL by ATP binding cassette 4 ABCA4

Question 30

What happens to transROL?

Answer 30

Transported to the RPE by inter-photoreceptor retinoid binding protein IRBP

Question 31

Once in the RPE, what chaperones transROL?

Answer 31

cellular retinol binding protein CRBP

Question 32

What happens to transROL in the RPE?

Answer 32

Esterified by lecithin-retinol acyltransferase LRAT - forming all-trans retinyl ester

Question 33

What is all-trans retinyl ester chaperoned by?

Answer 33

RPE65

Question 34

What is all-trans retinyl ester converted to, and by what?

Answer 34

11-cis-retinol by isomohydrolase.

Question 35

What is 11-cis-retinol chaperoned by?

Answer 35

Cellular retinaldehyde binding protein CRalBP

Question 36

What happens to 11-cis-retinol?

Answer 36

Oxidised by 11-cis-retinol dehydrogenase to 11-cis-retinal

Question 37

What returns 11-cis-retinal to the photoreceptor?

Answer 37

IRBP

Question 38

Cones have an alternate pathway for chromophore recycling vs rods. Which is faster, and why does this pathway exist?

Answer 38

Cones are faster, and this pathway is due to cones having 11-cis-retinol dehydrogenase

Question 39

Where are recycled retinoids stored? What happens if this store runs out?

Answer 39

In the RPE unless needed. Replenished from the choriocapillaris if depleted.

Question 40

Can mammalian rods convert 11-cis-retinol to 11-cis-retinal? What about cones?

Answer 40

Rods cant, it must occur in the RPE.

Cones can, they have 11-cis-retinol dehydrogenase

Question 41

What arrangement of chromophore will allow maximum efficiency in absorption?
Are mammalian photoreceptors arranged in a specific way?

Answer 41

Along the same axis as polarised light.

Mammalian cells arranged randomly, sensitive to non-polarised light.

Question 42

Summarise recycling.

Answer 42

-11-cis-retinal to all-trans retinal by light
-transRAL reduced to tROL by all-trans retinol dehydrogenase using NADPH
-tROL to transROL by ATP binding cassette 4
-transROL transported to RPE by inter-photoreceptor retinoid binding protein IRBP
-transROL chaperoned by CRBP
-transROL esterified by lecithin-retinol acyltransferase to all-trans retinyl ester
-all-trans retinyl ester chaperoned by RPE65
-all-trans retinyl ester converted to 11-cis-retinol by isomohydrolase
-11-cis-retinol chaperoned by CRalBP
-11-cis-retinol oxidised by 11-cis-retinol dehydrogenase to 11-cis-retinal
IRBP returns 11-cis-retinal to photoreceptor, recombines with opsin

Question 43

Name 2 diseases caused by mutations resulting in impaired RPE.

Answer 43

Mutation to RPE65

Mutation to ABCR