Exam 2 Koh- Retina Biochem 4 Flashcards
1
Q
What is important to RPE function?
A
Proteins, lipids, and nucleic acids
2
Q
____% of wet weight of the retina is water
A
> 80
3
Q
What is the primary carbon source used for energy?
A
Glucose
4
Q
Glucose is not converted to _______ in the RPE
A
Glycogen
5
Q
Nearly ______ proteins have been identified in RPE
A
850
6
Q
What gene is RPE specific
A
RPE 65
7
Q
______ compose of ~3% of the wet weight of the RPE
A
Lipids
8
Q
______% of wet weight are phospholipids with PC and PE
A
5
9
Q
Higher saturated FAs in the RPE include what?
A
Palmitic/stearic acid
10
Q
About 1% of the wet weight of the RPE is contributed by _____
A
RNA
11
Q
Retinal pigment epithelium is a single layer of cells with what type of junction?
A
Tight
12
Q
The RPE is a single layer of _____ epithelial cells
A
Columnar
13
Q
Where is the outermost layer of the retina located?
A
Between the choroid and outer segments
14
Q
How many RPE cells per eye?
A
4-6 million
15
Q
What is the ratio of photoreceptor cells to RPE cells?
A
45:1
16
Q
Epithelial cells are polarized with long ____ microvillous processes interdigitating the outer segment, and____ aspects adjacent to Bruch’s membrane
A
Apical, basal
17
Q
What serves as a blood-retinal barrier?
A
Polarized cells in the RPE
18
Q
What are the retinal pigment epithelium functions?
A
Light absorption, epithelial transport, glia, visual cycle, phagocytosis, secretion
19
Q
How does the RPE increase optical quality?
A
Forming a dark pigmented wall, aids in absorption of scattered light
20
Q
Blood perfusion of the choriocapillaris is ____ than the kidney
A
Higher
21
Q
Venous blood from the choriocapillaris shows ___% O2 saturation
A
90
22
Q
By comparison, venous blood from retinal vessels shows a O2 saturation of ____%
A
45
23
Q
What is OCA?
A
Oculocutaneous albinism
24
Q
OCA1 and OCA2 are due to defects in what?
A
The tyrosinase gene and the pink-eyed dilution gene
25
What happens when melanin levels are below a critical level?
Lack of foveal development, low vision, nystagmus and stabismus
26
What is the RPEs 3 lines of defense against toxins?
Light absorption, antioxidants and repairment
27
There is absorption and filtering of light via melanin in ________
Melanosomes
28
There is additional light absorption in the RPE by what 3 things?
Carotenoids, lutein, and zeaxanthin
29
What does blue light do in the RPE?
Permits the photoxidation of lipofuscin components to cell toxic substances
30
Lipofuscin ______ in the RPE during life
Accumulates
31
Lipofuscin might first be ____ for visual function
Beneficial
32
The RPE contains high amounts of what?
Superoxide dismutase and catalase
33
The RPE accumulates what?
Carotenoids (lutein and zeaxanthin), ascorbate, alpha-tocopherol, and beta-carotene; this is supplemented by glutathione and melanin, which itself can function as an antioxidant
34
What leads to retinal degeneration?
Increasing imbalance of protective and toxic factors
35
What is the most common cause for blindness in industrialized countries?
AMD
36
What is AMD?
An accumulation of lipofuscin in the RPE, a reduction in the cell density of RPE cells, a reduction in an important antioxidants, alpha-tocopherol
37
What happens to the organelles in AMD?
Age-related changes in pigmentation, age-dependent reduction of melanosomes, melanolysosomes (a sign of melanin degradation and melanolipofuscin granules)
38
What happens due to oxidative stress in Bruch's membrane?
Accumulation of AGEs
39
AGEs play an important role in what?
Induction of choroidal neovascularization
40
What is VEGF?
The major angiogenic factor in CNV in response to AGE exposure
41
What is produced when RPE can't convert all all-trans-retinol into 11-cis-retinal?
A2E
42
What does A2E do?
Increases the sensitivity of the RPE to blue light and has several toxic effects
43
Coupled with oxygen, A2Eis converted by ____ light into A2E-epoxides
Blue
44
What do A2E epoxides do?
Destabilize mitochondrial membrane and lysosomal membranes
45
A2E epoxides can inhibit ___ ___ in the respiratory chain
Cytochrome oxidase
46
What does A2E produce?
More reactive oxygen species
47
What is A2E?
N-retinylidene-N-retinylethanolamine
48
Loss of RPE cells denotes the beginning of the formation of what?
Drusen
49
What is the most important sign of AMD?
Drusen
50
What does drusen consist of?
Basal laminar deposits that are located between RPE and Bruch's membrane and basal linear deposits that are located inside Bruch's membrane
51
Metabolic waste products in the RPE include what?
Metbolic end prodcuts: lipoproteins and other hydrophobic material from both photoreceptors and RPE
52
What happens in the end stages of AMD?
The end stages of the disease are either geographic atrophy (GA), a loss of RPE and photoreceptors over large areas, or CNV with subsequent intraocular bleeding and formation of a disciform scar
53
What were the conclusions of the AREDS study?
Antioxidant vitamins and zinc therapy reduced the risk of developing advanced AMD in participants with intermediate and greater risk of developing AMD (categories 3 and 4) by 25%, antioxidants and zinc are now recommended for participants who have an intermediate risk of developing advanced AMD
54
The RPE transports nutrients and ions between what two layers?
Photoreceptors and choriocapillaris
55
____ leads to a movement of water from the vitreous body into the retina
IOP
56
Water in the inner retina is transported by ____ cells and water in the _____ ____ is eliminated by the RPE
Muller, subretinal space
57
What is required for an adhesive force between RPE and the retina?
Water transport
58
Where does the RPE transport ions and water?
From the subretinal space or apical side to the blood or basolateral side
59
The RPE has the structural properties of an ___ ____ ____
Ion transporting epithelium
60
Tight junctions establish a barrier between what 2 layers?
Subretinal space and choriocapillaris
61
Where are the majority of mitochondria located in the RPE?
Basolateral side
62
Where is the Na-K-ATPase located in the RPE? Function?
Located in the apical membrane, provides the energy for transepithelial transport
63
What do the Cl and K transports do in the RPE?
At the apical membrane this gradient facilitates uptake of HCO4 via the Na-HCO3 cotransporter and uptake of K and Cl via the Na-K-2Cl cotransporter
64
How does the RPE transport glucose?
RPE contains high amounts of glucose transporters in both the apical and the basolateral membranes
65
How is vitamin A (all-trans-retinol) taken up from the bloodstream?
Via a receptor-mediated process with recognition by a serum retinol-binding protein/transthyretin (RBP/TTR) complex
66
What are the factors of retinal adhesion?
Passive hydrostatic forces, interdigitation of outer segments and RPE microvilli, active transport of subretinal fluid, and the complex structure and binding properties of the interphotoreceptor matrix
67
What is the net rate of fluid transport across the RPE?
4-6 microliters per cm^2 per hour
68
Clinical RPE detachments may result from what?
Breakdown of the transport mechanisms for fluid across the RPE as a result of focal damage
69
What is the space between the RPE and photoreceptors?
IPM
70
What does the IPM do?
Mediates adhesion between the RPE and photoreceptor layer, phagocytosis by the RPE and nutrient exchange between RPE and the photoreceptors
71
What is the composition of the matrix?
Interphotoreceptor retinal binding protein, basic fibroblast growth factor (bFGF), hyaluronan and hyaluronan binding proteoglycans, sulfated glycosaminoglycans and matrix metalloproteases
72
Delivery of ______ ____ to photoreceptors is a third kind of transport of importance for visual function
Docosahexaenoic acid
73
Membranes of neurons and photoreceptors are selectively built from ________
Phospholipids
74
How does the RPE take up docosahexaenoic acid?
Concentration-dependent manner
75
Photoreceptor outer segments are newly built from the _____ of outer segments, at the ____
Base, cilium
76
What is at the tip of POS?
Highest concentration of radicals, photo-damaged proteins, and lipids are phagocytosed by the RPE
77
What is recycled to photoreceptors?
Retinal or docosahexaenoic acid
78
In the processof phagocytosis, every RPE cell is facing an average ranging between what?
20-45 photoreceptors
79
The turnover rate for one entire photoreceptor outer segment is what?
10-14 days
80
What growth factors does the RPE secrete?
Fibroblast growth factors (FGF-1, FGF-2, and FGF-5), transforming growth factor- (TGF-beta), insulin-like growth factor-I (IGF-I), ciliary neurotrophic factor (CNTF), platelet-derived growth factor (PDGF), VEGF, lens epithelium-derived growth factor (LEDGF), members of the interleukin family and pigment epithelium-derived factor (PEDF)
81
What is PEDF?
To protect neurons against glutamate-induced or hypoxia induced apoptosis, antiangiogenic factor that inhibits endothelial cell proliferation, abnormal growth factor regulation contributes CNV
82
What is VEGF?
Secreted in low concentrations by the RPE in the healthy eye, prevents endothelial cell apoptosis and is essential for an intact endothelium of the choriocapillaris, also acts as a permeability factor stabilizing the fenestrations of the endothelium
83
VEGF is ____ side, PEDF is ____ side
Basolateral, apical
84
RPE sits on what prominent basement membrane?
Bruch's membrane
85
How many layers is Bruch's membrane?
5
86
What does Bruch's membrane consist of?
Proteoglycans, matrix proteins, hyaluronic acid, chondroitin sulphate plus types I, III, VI, and VII collagen, and elastin
