Block 11 Flashcards
What is RPE
A monolayer of pigmented cells
Where is RPE located
Between choriocapillaris and outer segment of photoreceptors
Whe apical side of the RPE faces
Photoreceptors
The basal side of RPE faces
Bruchs membrane
General Light absorption in the RPE is due to
Melanin
Blue light is absorbed in the RPE due to
Lutein and zeaxanthin
What damage does RPE protect from
Oxidative damage
T/F the outer retina is exposed to an oxygen -rich environment
True
What does the RPE transport nutrients and wastes between
Photoreceptors and choriocapillaris
What are the 2 divisions of transepithelial transport in RPE
Transport from photoreceptors to blood
Transport from blood to photoreceptors
How is water removed from the RPE
It is active transport driven by an active transport of Cl from the retina to blood side
What is Best’s Vitelliform Macular Degeneration
Degeneration of RPE
Bulls eye lesion
Lesion composed of extracellular fluid
There is a reduction in epithelial Cl- transport
What is required to removal of lactic acid from apical side
Tight regulation of intracellular pH
What are some other substances that are transported to blood to photoreceptor
Glucose
All-trans-retinol
DHA
Where does the reduction of all-trans-retinAl into all-trans-retinOl occur
Photoreceptors
Where does the reisomerization of all-trans-retinOl into 11-cis-retinAl occur
RPE
What causes retinitis pigmentosa
Mutations in the Genes of the visual cycle
There is an inability of the RPE to phagocytose photoreceptor outer segment
What causes Stargardt disease
Mutations in the genes of the visual cycle
What is phagocytosis controlled by
Circadian control
It is triggered by the onset of light in the morning
RPE cell faces an average of ___ photoreceptors in the fovea
23
Every ___ days a whole length of photoreceptor outer segment is renewed
11
What is Usher syndrome
A defect of RPE photoreceptor phagocytosis
Causes retinal degeneration in Usher type 1B patients
PEDF does
Antiangiogenic factor
Inhibits endothelial cell proliferation
Stabilizes the endothelium of the choriocapillaris
VEGF does
Low concentrations in healthy eye
Prevents endothelial cell apoptosis
Stabilizes the endothelium in the choriocapillaris
What are some other factors that the RPE secrete
- Growth factors
- factors that maintain structure of retina
- cytokines or immune modulators
What happens in choroidal neovascualrizations
RPE cells secreted VEGF at a higher rate
Most severe complication in age-related MD
What is the retinal-blood barrier
Tight junctions between retinal pigment epithelium
What is photoreception
Light detection that leads to vision
What does photoreception depend on
Photoreceptors
What is photon absorption done by
Visual pigment that is lying on one of the discs in the outer segment of the photoreceptors
What is scotopic (peripheral vision)
Dim light
Motion
What is photopic (central) vision
Color
Detail
Scotopic vision utilizes
Rods
Photopic vision utilizes
Cones
Describe rods
Not good for detail No color Very sensitive Good for dim Lower sensitivity to rapidly changing stimuli
Describe cones
Specialized for detail
Color vision
Less sensitive
Higher sensitivity for rapidly changing stimuli
T/F there are rods in the fovea
False
Where is the peak for cones
Fovea
Rods comprise of ____ of photoreceptors
97%
What is the rod peak wavelength sensitivity
500-510 nm
Rod convergence increases ______
Sensitivity
Cones are ____ of photoreceptors
3%
Where are their more cones
In the periphery
What are the 3 different cones
Red
Blue
Green
Red cone
L cone
Long wavelength
Green cone
M
Medium wavelength
Blue cone
S
Short wavelength
T/F there is convergence in the fovea
False
What are photopigments
Unstable pigments that undergo a chemical change when they absorb light
What makes up photopigments
Protein(opsin) + chromophore
What is rhodopsin
Opsin + 11-CIA-retinAl
What is rhodopsin used for
Dim light vision
Describe rhodopsin
Insoluble in water
More stable than cone pigments
More abundant
What are the 3 different iodopsins
Erythrolabe
Chlorolabe
Cyanolabe
What is the max absorption of erythrolabe
Yellow/red (L cones)
What is the max absorption for chlorolabe
Green
M cones
What is the max absorption for cyanolabe
Bluefish/violet
S cones
What makes up erythrolabe
Photopsin I + 11-cis-retinal
What makes up chlorolabe
Photopsin II + 11-is-retinal
What makes up cyanolabe
Photopsin III + 11-CIA-retinal
What is phototransduction
Series of biochemical events that lead from photon capture by a photoreceptor cell to its hyperpolarization and slowing of neurotransmitter release at the synapse.
It is essentially the transformation of light into electrical and chemical signals that produce the perception of light
What are the steps of phototransduction
Photoreception> biochemical cascade> electronic spread> slowing of neurotransmitter release
What channel closes in phototransduction
CNG channel
What is the CNG channel
Cyclic GMP gated cation channel
What does CNG channel do
Allow NA and K and Ca to enter the cell
Cell will be partially depolarized
What is the dark current
Flow of cations into and out of the cell while in the dark
Know diagram on lecture 2 slide 18
Biochemical cascade
Where does the reduction of all-trans-retinal into all-trans-retinol occur
Photoreceptors
Where does the reisomerization of all-trans-retinol into 11-cis-retinal occur
RPE
Look over the G protein activation on slide 21
Confusion
Step 3 is PDE6 activation
Activated G protein binds with a molecule named cGMP phosphodiesterase PDE6
PDE6 converts cGMP into GMP
Step 4 is channel closing
Reduction of cGMP concentration causes CNG channel closure
What does closing of the Channels do
Reduces the flow of NA and Ca ions in the cell
Reduces the dark current and makes membrane potential more -
What is the photocurrent in the dark
Cations move into the cell
What is the photocurrent in light
A single photo isomerization closes ion channels and causes a 2% reduction in the photocurrent
How do Rhodes communicate with downstream bipolar cells
Glutamate
What does a high level of glutamate release signal
Darkness
What causes a reduction in the level of glutamate due to
Absorption of light
What is adaptation
Alters sensitive to light
Decreases sensitive to bright
Increases sensitivity to dim light
Controlled by Ca influx
What are the major energy producing metabolic pathways
Glycolysis
TCA
ETC
What are the sources of metabolites for the retina
Glycogen stores (retina)
Glucose (aqueous)
Amino acids (aqueous)
Saturated and unsaturated fatty acids (aqueous)
How is glucose delivered
Derived from the serum
Simple diffusion into the aqueous
What is the glucose level in the aqueous due to
There is a constant flux of glucose from the plasma in t het aqueous
What is the aqueous glucose level compared to serum glucose
80%
What contributes to the production of lactic acid (even in aerobic conditions)
Glucose metabolism of RETINA, ciliary epithelium, lens, cornea
Why doesn’t lactic acid accumulate in the aqueous
There is quick trafficking away from the aqueous
When is the most lactic acid made
During sleep of conditions that block atmospheric O2 from being absorbed by the eye
(Topical epinephrine in the eye)
Where does the eye get O2 from
Atmosphere
Vitreous
How is the O2 concentration in the vitreous from posterior to anterior
Higher posterior
Anterior is lower
What does the vitreous serve as for the retina
An metabolic reservoir
Provides short-term nutrients during emergencies
What is ascorbic acid
High levels in the vitreous
Vitreous to serum 9:1
Concentrated by active transport in ciliary epithelium
Supplied by the diet
What are the reasons for high ascorbic acid
- Absorb UV light
- Free radical scavenger
- Protect against oxidative damage from inflammation
- protect the retina and lens from metabolic and light induced production fo singlet oxygen
What is the evidence for the benefits of ascrobic acid
Supplements in dark-reared rats reduce irreversible type 1 light damage
And shift the light damage to reversible the 2 light damage
What is the implication of ascorbic acid in inflammation
Ascorbic acid synthesis is unregulated in repsonse to inflammatory mediators such as histamine
What transporter is responsible for the transport of glucose to the retina
GLUT3
What transporter is insulin dependent and thus is NOT found in the retina
GLUT 4
When the eye s subject to endotoxins that produce an inflammatory response what will protect the eye
Ascorbic acid
What is a synapse
A junction between 2 nerve cells
Consists of a minute gap across which impulses pass by diffusion of a NT
What type of NT is glutamate
excitatory
What type of NT are GABA and Glycine
Inhibitory
What is hyperpolarization
Makes cell membrane potential MORE NEGATIVE
Inhibits AP
What is depolarization
Makes cell membrane potential more negative
What are light-evoked signals transferred onto
Bipolar and horizontal cells
What do horizontal cells provide interactions to
Lateral interactions in the OPL
Where do bipolar cells transmit there signals to
IPL onto amacrine and ganglion cells
What role do ganglion cells play in light transmission
They collect signals from bipolar and amacrine cells and transmit these signals to the visual centers in the brain
What is the NT at the cone pedicle
Glutamate
When is glutamate high
In darkness
It is reduced by light
OFF cone bipolar cells and horizontal cells are _______ by light
Hyperpolarized
ON cone bipolar cells are _______ by light
Depolarized
OFF cone bipolar cells transfer signals into….
OFF ganglion cells
ON cone bipolar cells transfer signal onto…..
ON ganglion cells
Describe the density of cones, bipolar cells, and ganglion cells in the retina
They increase in number towards the center of the retina
How do the retina cells at the center of the retina compare to those in the periphery
In the center they are smaller
In the periphery they gradually increase in size
What causes the high VA in the central retina
High cone density
Low cone to RGC ratio
What is the midget system
On e cone connected to a midget bipolar cell connected to a midget ganglion cell (1:1)
What is the NT of the rod spherule
Glutamate
When is glutamate high
In darkness
What is the only type on rod bipolar cell
ON rod bipolar cells
ON rod bipolar cells are _____ by light
Depolarized
What is the rod pathway
Rod> ON rod bipolar cell (depol) > amacrine (depol) >
1) On cone bipolar the ON ganglia (glutamte)
2) Off cone bipolar > OFF ganglion cell (glycine)
How do horizontal cells produce feedback in rods
They modulate the glutamate release by shifting the activation curves of the rod spherule Ca2+ channels
Release GBA providing inhibition of bipolar cell dendrites
How do horizontal cells provide feedback for cones
Modulate the release of glutamte by shifting hot activation curves of the cone pedicab Ca2+ channels
What are glutamatergic neruons
Rods
Cones
Bipolar cells
Most ganglion cells
What are GABAergic and Glycinergic neurons
Horizontal cells
Most amacrine cells
How does the optic nerve change with age
Nerve fibers decrease
Optic cup diameter increases
How does the ILM change with age?
What affect does this have?
Thickens
Dimmer foveal reflex
How does RPE change with age
Total number of RPE decreases
Lipofuscin in RPE increases
Drusen increases
What change occurs in aging across the entire retina
Atrophy increases
What is a Tigris fundus
Age related retinal atrophy
Pigmentation in RPE/choroid decreases
What is reticular degeneration
Age related retinal atrophy
Peripheral RPE degeneration
Is there blood flow in the lens
No
Is there innervation in the lens
No
How does the lens grow
It grows in size throughout life and does not shed cells
What can disrupt lens clarity
Accumulated post synthesis modified components
Several types of accumulated materials give rise to cataract types
What is the lens composed of
Water
Protein
Lipids/cholesterol
Most simple sugars can be metabolized, but which one is most predominant
Glucose
Does the lens metabolize lipids and amino acids
Yes, they are incorporated in to structural components
Describe anaerobic glycolysis of the lens
The most active energy metabolism in the lens
Provides 70%
What does the HMP shunt do in the lens
Secondary producing NADPH and -10% of lens energy
Where does the rest of the 20% come from
It is derived from the metabolism of lactic acid and the glucose in lens epithelium cells that utilize the TCA and ET
Since the lens has no blood supply where does it get its glucose from
The posterior or anterior lens surfaces that contacts other mediums such as the aqueous humor
How is glucose taken up by the aqueous
Facilitated diffusion
How is the transport of glucose among lens cells accomplished
A network of low resistance gap junctions between cells
This allows for efficient distribution of glucose, even to lens buried deep toward the center of the lens
Is the ens affected by anaerobic conditions?
It is unaffected because of its reliance on anaerobic glycolysis for energy
How are wastes removed from the lens
What are some examples of wastes removed
Ex. Lactic acid
It is removed at a steady rate via diffusion to aqueous humor and then to blood stream
How does the anterior Y suture appear
Y
How does the posterior Y suture appear
An upside down Y
What are the functions of the lens
- Refracts light to be focused on the retina
- 1/3 D power of eye (15D)
- allows accommodation of near objects
- absorbs UV lights and thus protects the retina from UV damage
What is the composition of the lens
Water (65%)
Proteins (35%)
Other stuff (1%)
What protein groups are contained in the lens
Water soluble (crystallins) Urea soluble (crystallins and cytoskeleton) Insoluble (membrane proteins)
What are the groups of crystallins
Alpha
Beta
Gamma
What do alpha crystallins do
Produce a phenomenon that contributes to lens transparency and gives the lens a significantly higher index of refraction than surrounding fluids
What does alpha crystallins provide resistance to
Degradation of the other crystallins beta and gamma
It is a molecular chaperone
What is important of the concentration of crystallin
It varies throughout the lens
Provides a refractive index gradient that is higher in the nucleus than the cortical surface
What is reduced in the lens due to gradient index system and peripheral flattening
Spherical aberration
What allows for transparency in the cellular level
Small lens fibers Uniformity of lens fibers Regular packing Paucity of organelles Avascular
What allows transparency at the molecular level
Proteins are uniform and small
The concentration increases towards the nucleus and creates an RI gradient that is higher in the nucleus than in teh cortical space
Hw does water contribute to the transparency of the lens
Water is pumped out of the lens from the anterior surface by Na/K pump
Water enters the lens from the back because the osmotic pressure
What is the mitotic activity of the lens
Mitosis of secondary fiber cells occurs in the germanitive zone of anterior lens epithelium
After mitosis, lens fiber cells gradually migrate through the transition zone and into the equator where elongation occurs
What is glutathione
Primary protector against oxidative damage in the lens
It is transported into the lens from the aqueous and can be synthesized from lens epithelial cells and superficial fiber cells
Glutathione detoxifies hydrogen peroxide
Where is ascobric acid higher
Has higher concentration in the lens than aqueous
How does accommodation decrease in old age
Ability of accommodation decreases by 1/4 of the age (Hofstetters formula)
What is age related nuclear cataract
Decline of glutathione, making the fibers susceptible to oxidative damage
Older nuclear fibers lose organelles and their nucleus and gain yellow-brown pigment
What is age related cortical cataract
Decrease in glutathione
Increase in Ca, Na, and water
Water forms a lake that separates cells and creates vacuoles. These create light scatter and the cells burst, proteins are exposed and oxidized. Forming a cataract
What is posterior subcapsular cataract
Epithelial like cells migrate from the equatorial region and accumulate in the posterior pole forming an opacity
What happens to crystallins with age
Decrease (especially alpha)
What happens to lens thickness with age
Thickens (0.22mm per year)
What happens to the anterior capsule with age
Posterior capsule?
Increases
Posterior: stable
What appends to the radius of curvature for anterior and posterior lens with age
Decreases
What happens to the center of the lens with age
Anterior chamber depth?
Center moves anterior with age
Anterior chamber depth decreases with age
What happens to the amino acids in the eye with age
Decreases
What is a diabetic cataract?
How does it form?
What accumulates?
Inclusion insensitive buildup of BG
There is an increase in sorbitol, osmotic pressure, and water. This causes swelling and a cataract will form
Depletion of NADPH during sorbitol production causes glutathione not being able to reduce free radicals so there will be an increase in oxidative stress.
Polymerization of proteins
How can there be changes in refractive error in the aging eye
Thickness Change, radius of curvature change, ex changes
Unusual changes in Rx May indicate uncontrolled diabetes
