Biochemistry and Metabolism- RPE Flashcards
(40 cards)
What is the function of the RPE
- vitamin A regeneration, which is integral to sustaining vision
- phagocytosis of shed photoreceptor outer-segment discs
- biological filter for the neurosensory retina through transport of necessary nutrients
and ions to photoreceptor cells and removal of waste products from photoreceptors - absorption of scattered and out-of-focus light via pigmentation
- adhesion of the retina
- secretion of humoral and growth factors
What does mutation of gene RPE65 lead to
Mutation of the gene RPE65, which encodes the enzyme (RPE65 isomerohydro- lase) that converts all-trans-retinyl ester to 11-cis-retinol, causes Leber congenital amaurosis (LCA). RPE65 is the target of a treatment approved by the US Food and Drug Administration (FDA) that uses an adeno associated virus to deliver the gene to the RPE of LCA patients
What is autophagy
cell degrades its own damaged components and recycles the products. In the RPE, this is essential for management of phagocytosed outer segments as well as for turnover of its components
What embrylogical layer is the RPE derived from
monolayer of neuroectoderm-derived epithelial cells located between the highly vascular choriocapillaris and the photoreceptor outer segments
How many RPE cells are there per eye
4–6 million RPE cells per eye
What forms the outer blood retinal barrier
On the apical surface of RPE cells are long microvilli that interdigitate with the outer segments of photoreceptor cells. These cells are joined near their apical side by tight junctions that establish polarity, block the passage of water and ions, and constitute the outer blood–retina barrier
What is Bruch Membrane composed of
an extracellular matrix between the RPE and the choriocapillaris), has many infoldings that increase the surface area available for the exchange of solutes
What key cells do RPE contain
Melanin and Phagosomes reflecting their role in light absorption and phagocytosis
Pathways used to generate energy in RPE
glycolysis, the Krebs cycle, and the pentose phosphate pathway
What is the majority of wet weight of RPE contributed by and how much?
Water- >80%.
Proteins, lipids and nucleic acids contribute the rest
How many proteins are identified in RPE
Nearly 850
What kind of proteins are found in RPE
Hydrolytic enzymes such as glutathione, peroxidase, catalase and superoxide dismutase important for detoxification
Cytoskeletal proteins such as actin, myosin, alpha actinin, fodrin and vinculin are also present in RPE and other cells
Where is the Na+/K+/ATPase found found on RPE
On the apical membrane in contrast to most polarized cells
Which RPE protein is exclusively expressed on the RPE and its function
RPE-specific protein 65 kDa (RPE65), is an obligate component of the isomerization and hydrolysis of vitamin A, which is required for regeneration of visual pigment (described later in Vitamin A Regeneration)
What % weight do lipids contribute of the weight of the RPE
3%- half are phospholipids
Which organ contains the highest concentration of vitamin A in the body
Liver, then RPE
What is RPE role in vitamin A regeneration
RPE supplies the photoreceptor outer segments with vitamin A, which is tethered to rhodopsin in rods and to the 3 different cone opsins (red, green, and blue). Regenerates all-trans retinal to cis-retinal for activation by light
How is free all-trans-retinal cleared from rod discs
ABCA4. After transport to cytosol from rod discs, all-trans-retinal is reduced to all-trans-retinol by retinol dehydrogenease
What is the phototransduction cascade
Retinal attaches to a lysine residue on rhodopsin. When the com- plex absorbs light, 11-cis-retinal transforms into all-trans-retinal via a process known as photo- isomerization. This induces a conformational change in the attached rhodopsin molecule, activating the second-messenger system and initiating the phototransduction cascade within the photoreceptor. The all-trans-retinal is shed from rhodopsin and transported by ABCA4 from the rod disc to the cytosol, where it is converted to all-trans-retinol. Then, all-trans-retinol is delivered to the RPE via interphotoreceptor retinoid-binding protein (IRBP), which acts as a shuttle and also shields the cell membranes from the membranolytic retinoid molecules. Once in the RPE, this molecule is esterified by lecithin retinol acyltransferase (LRAT). The resultant retinyl ester is converted to 11-cis-retinol by the isomerohydrolase RPE65. 11-cis-Retinol is then oxidized to 11-cis-retinal by retinol dehydrogenase (RDH) and shuttled back to the photoreceptor outer-segment discs by IRBP to participate in another visual cycle
What conditions are associated with mutation of ABCR gene
ABCR gene encodes ABCA4 transporter protein leads to Stargadt disease.
What conditions are associated with mutation of RPE65 gene
Leber congenital amaurosis
How many outer segment discs are shed per day
100 from each photoreceptor cell. Many photoreceptors interdigitate with a single RPE cell, each RPE cell digests more than 4000 discs daily
When are discs shed
Shedding most vigorous at dawn in rods
Shedding most vigorous at dusk in cones
What happens to the shed outer segment discs
encapsulated in phagosomes which in turn fuse with lysosomes and are digested. During degradation of the discs, building blocks are recycled into photoreceptors for use in the synthesis and assembly of new discs
