BS - Bleaching and Recycling - Week 10 Flashcards
What are RPE cells and where are they located?
Monolayer of pigmented cells located between choricapillaris and photoreceptors
Name 6 functions of RPE cells.
- 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)
How many photoreceptors does each RPE cell form a functional unit with?
Around 23 photoreceptors
What are the 2 components of photopigments, and where are they synthesised?
Opsin and chromophore
Consider the components of a photopigment. What is the origin of each?
Chromophore - not made in the body, is derived from the diet.
Opsin - synthesised in the inner segment
What are the 2 isomeric forms of retinal? And what causes them to change to the other?
11-cis and all-trans - converts to all-trans in response to light
All-trans is a straighter molecule
What are some source of vitamin A?
B-carotene and vitamin A precursors from diet
Red/yellow vegetables, fish, dairy, eggs
What is a retinoid?
Any derivative of vitamin A.
What are the three active forms of vitamin A?
Retinal, retinol, and retinoic acid.
In what form is vitamin A stored?
Retinyl ester.
What two forms of retinoids can be readily interconverted?
Retinal and retinol.
Where are retinyl esters typically found (2)?
Rich in the liver, also found in circulating chylomicrons
What are retinyl esters complexed with in the bloodstream?
Transthyretin
What happens if you eat a polar bear liver?
Le khod
What happens to beta-carotene when eaten, and how? What does it form?
It is solubilised by bile salts and lipolytic enzymes into retinol.
When beta-carotene is eaten, how is it transported out of the intestines?
Once converted to retinol, it binds to cellular retinol binding protein, CRBP, and is transported out.
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?
Retinyl esters are incorporated into chylomicrons.
They can bind to the RPE, but is a minor source.
In what 3 forms are retinoids stored in the liver?
Chylomicrons
Retinyl esters
Retinol palmitate
Is vitamin A susceptible to oxidation or reduction?
Oxidation
When not in retinyl ester form, what are retinoids always bound to?
Retinoid binding protein RBP
How do retinoids avoid being filtered by the kidneys?
Retinoids and RBP complex with transthyretin
Where do retinol-transthyretin complexes end up?
They bind to retinoid binding protein receptors on the RPE.
What are the two sources of retinoids for the RPE, and which is major/minor?
Major - retinol-transthyretin complex binding to receptors on the RPE.
Minor - retinyl esters in chylomicrons reaching the RPE through the bloodstream.
In what form is vitamin A within the RPE?
Retinyl ester.
Can the retina function without vitamin A?
Yes
What can vitamin A deficiency lead to (2)?
Night blindness
Dry eye
What happens to the chromophore after it photoisomerises to all-trans retinal?
It separates from the opsin for recycling.
What happens to all-trans retinal after it detaches from the opsin?
Is reduced to all-trans retinol via all-trans retinol dehydrogenase, requiring NADPH
What happens to tROL?
Converted to transROL by ATP binding cassette 4 ABCA4
What happens to transROL?
Transported to the RPE by inter-photoreceptor retinoid binding protein IRBP
Once in the RPE, what chaperones transROL?
cellular retinol binding protein CRBP
What happens to transROL in the RPE?
Esterified by lecithin-retinol acyltransferase LRAT - forming all-trans retinyl ester
What is all-trans retinyl ester chaperoned by?
RPE65
What is all-trans retinyl ester converted to, and by what?
11-cis-retinol by isomohydrolase.
What is 11-cis-retinol chaperoned by?
Cellular retinaldehyde binding protein CRalBP
What happens to 11-cis-retinol?
Oxidised by 11-cis-retinol dehydrogenase to 11-cis-retinal
What returns 11-cis-retinal to the photoreceptor?
IRBP
Cones have an alternate pathway for chromophore recycling vs rods. Which is faster, and why does this pathway exist?
Cones are faster, and this pathway is due to cones having 11-cis-retinol dehydrogenase
Where are recycled retinoids stored? What happens if this store runs out?
In the RPE unless needed. Replenished from the choriocapillaris if depleted.
Can mammalian rods convert 11-cis-retinol to 11-cis-retinal? What about cones?
Rods cant, it must occur in the RPE.
Cones can, they have 11-cis-retinol dehydrogenase
What arrangement of chromophore will allow maximum efficiency in absorption?
Are mammalian photoreceptors arranged in a specific way?
Along the same axis as polarised light.
Mammalian cells arranged randomly, sensitive to non-polarised light.
Summarise recycling.
-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
Name 2 diseases caused by mutations resulting in impaired RPE.
Mutation to RPE65
Mutation to ABCR
