Flashcards in Exam 2 Koh- Retina Biochem 4 Deck (86):
What is important to RPE function?
Proteins, lipids, and nucleic acids
____% of wet weight of the retina is water
What is the primary carbon source used for energy?
Glucose is not converted to _______ in the RPE
Nearly ______ proteins have been identified in RPE
What gene is RPE specific
______ compose of ~3% of the wet weight of the RPE
______% of wet weight are phospholipids with PC and PE
Higher saturated FAs in the RPE include what?
About 1% of the wet weight of the RPE is contributed by _____
Retinal pigment epithelium is a single layer of cells with what type of junction?
The RPE is a single layer of _____ epithelial cells
Where is the outermost layer of the retina located?
Between the choroid and outer segments
How many RPE cells per eye?
What is the ratio of photoreceptor cells to RPE cells?
Epithelial cells are polarized with long ____ microvillous processes interdigitating the outer segment, and____ aspects adjacent to Bruch's membrane
What serves as a blood-retinal barrier?
Polarized cells in the RPE
What are the retinal pigment epithelium functions?
Light absorption, epithelial transport, glia, visual cycle, phagocytosis, secretion
How does the RPE increase optical quality?
Forming a dark pigmented wall, aids in absorption of scattered light
Blood perfusion of the choriocapillaris is ____ than the kidney
Venous blood from the choriocapillaris shows ___% O2 saturation
By comparison, venous blood from retinal vessels shows a O2 saturation of ____%
What is OCA?
OCA1 and OCA2 are due to defects in what?
The tyrosinase gene and the pink-eyed dilution gene
What happens when melanin levels are below a critical level?
Lack of foveal development, low vision, nystagmus and stabismus
What is the RPEs 3 lines of defense against toxins?
Light absorption, antioxidants and repairment
There is absorption and filtering of light via melanin in ________
There is additional light absorption in the RPE by what 3 things?
Carotenoids, lutein, and zeaxanthin
What does blue light do in the RPE?
Permits the photoxidation of lipofuscin components to cell toxic substances
Lipofuscin ______ in the RPE during life
Lipofuscin might first be ____ for visual function
The RPE contains high amounts of what?
Superoxide dismutase and catalase
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
What leads to retinal degeneration?
Increasing imbalance of protective and toxic factors
What is the most common cause for blindness in industrialized countries?
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
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)
What happens due to oxidative stress in Bruch's membrane?
Accumulation of AGEs
AGEs play an important role in what?
Induction of choroidal neovascularization
What is VEGF?
The major angiogenic factor in CNV in response to AGE exposure
What is produced when RPE can't convert all all-trans-retinol into 11-cis-retinal?
What does A2E do?
Increases the sensitivity of the RPE to blue light and has several toxic effects
Coupled with oxygen, A2Eis converted by ____ light into A2E-epoxides
What do A2E epoxides do?
Destabilize mitochondrial membrane and lysosomal membranes
A2E epoxides can inhibit ___ ___ in the respiratory chain
What does A2E produce?
More reactive oxygen species
What is A2E?
Loss of RPE cells denotes the beginning of the formation of what?
What is the most important sign of AMD?
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
Metabolic waste products in the RPE include what?
Metbolic end prodcuts: lipoproteins and other hydrophobic material from both photoreceptors and RPE
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
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
The RPE transports nutrients and ions between what two layers?
Photoreceptors and choriocapillaris
____ leads to a movement of water from the vitreous body into the retina
Water in the inner retina is transported by ____ cells and water in the _____ ____ is eliminated by the RPE
Muller, subretinal space
What is required for an adhesive force between RPE and the retina?
Where does the RPE transport ions and water?
From the subretinal space or apical side to the blood or basolateral side
The RPE has the structural properties of an ___ ____ ____
Ion transporting epithelium
Tight junctions establish a barrier between what 2 layers?
Subretinal space and choriocapillaris
Where are the majority of mitochondria located in the RPE?
Where is the Na-K-ATPase located in the RPE? Function?
Located in the apical membrane, provides the energy for transepithelial transport
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
How does the RPE transport glucose?
RPE contains high amounts of glucose transporters in both the apical and the basolateral membranes
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
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
What is the net rate of fluid transport across the RPE?
4-6 microliters per cm^2 per hour
Clinical RPE detachments may result from what?
Breakdown of the transport mechanisms for fluid across the RPE as a result of focal damage
What is the space between the RPE and photoreceptors?
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
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
Delivery of ______ ____ to photoreceptors is a third kind of transport of importance for visual function
Membranes of neurons and photoreceptors are selectively built from ________
How does the RPE take up docosahexaenoic acid?
Photoreceptor outer segments are newly built from the _____ of outer segments, at the ____
What is at the tip of POS?
Highest concentration of radicals, photo-damaged proteins, and lipids are phagocytosed by the RPE
What is recycled to photoreceptors?
Retinal or docosahexaenoic acid
In the processof phagocytosis, every RPE cell is facing an average ranging between what?
The turnover rate for one entire photoreceptor outer segment is what?
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)
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
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
VEGF is ____ side, PEDF is ____ side
RPE sits on what prominent basement membrane?
How many layers is Bruch's membrane?