B11 Flashcards
The RPE is a monolayer of pigmented cells, located between _________ and ________
Choriocapillaris and outer segments of photoreceptors
The apical membrane of the RPE faces the photoreceptor _______
Outer segments
What surrounds the light sensitive outer segments of the RPE?
Long apical microvilli
The _____ membrane faces Bruchs membrane
Basolateral
Light energy is concentrated on the?
Retina
General light absorption occurs via ____ in RPE
Melanin
Blue light absorption is supplemented by ___ and ___ in photoreceptors
Lutein and zeaxanthin
What is the most dangerous light to the RPE?
Blue light
The outer retina is exposed to what kind of environment?
Oxygen rich
T/F: The blood perfusion of the choriocapillaris is very high in the outer retina
True
Venous blood from the choriocapillaris shows a ___% O2 saturation
90%
RPE contains high amounts of superoxide dismutase and catalase
Enzymatic antioxidants
RPE accumulates lutein and zeaxanthin, ascorbate, alpha-tocopherol and beta-carotene
Non-enzymatic antioxidants
The RPE transports nutrients and metabolic end products
between ______and the _______
Photoreceptors and choriocapillaris
Is blood on the apical or basolateral side?
Basolateral
Are the photoreceptors on the apical or basolateral side?
Apical
The space between RPE and photoreceptors
Subretinal space
What are the two ways of transport in the RPE?
Photoreceptors—>blood
Blood—>photoreceptors
The transport of water is driven by _______ of Cl- from the retina to blood side
Active transport
Describe Bests Vitelliform Macular Degeneration
- Degeneration of RPE
- Bull’s eye shaped lesion
- The lesion primarily contains extracellular fluid
- Reduction in epithelial Cl- transport
The transport of lactic acid requires a tight regulation of the ______PH
Intercellular
The RPE contains an abundance of what 2 glucose transporters?
GLUT1 and GLUT3
An important substance of building membranes of neurons, photoreceptors as well as photoreceptor disk membrane
Docosahexaenoic acid (DHA)
What two things are removed from the apical side?
Water and lactic acid
The reduction of all-tran retinal into all trans-retinol occurs where?
In photoreceptors
Reisomerization of all-trans-retinol into 11-cis-retinal occurs in?
The RPE
Describe retinitis pigmentosa
- inherited retinal degeneration
- mutations in genes of the visual cycle
- inability of the RPE to phagocytose photoreceptor outer segments
Describe stargardt disease
- retinal degeneration
- mutations in the genes of the visual cycle
The process of phagocytosis is under what kind of control?
Circadian control
What triggers phagocytic activity?
The onset of light in the morning
Every RPE cell is facing an average of _____ photoreceptors in the fovea
23
When does the whole length of a photoreceptor outer segment get renewed?
Every 11 days
What must occur in order to keep excitability of photoreceptors ?
The tips of photoreceptor outer segments that contain the highest concentration of photo-damaged substances are shed from photoreceptors
Shed photoreceptor outer segments are phagocytosized by?
RPE
A defect of RPE photoreceptor phagocytosis may also cause retinal degeneration in usher type 1B patients
Usher syndrome
What are the 3 actions of PEDF?
- Antiangiogenic factor
- Inhibits endothelial cell proliferation
- Stabilizes the endothelium of the choriocapillaris
What is secreted in low concentrations in the healthy eye?
VEGF
Name 2 actions of VEGF
- Prevents endothelial cell apoptosis
- Stabilizes the endothelium of the choriocapillaris
What are some other factors that are essential for maintenance of the structural integrity of the retina?
- TIMP1
- TIMP3
The most severe complication in age-related macular degeneration
Choroidal neovascularization
In choroidal neovascularization, do RPE cells secrete VEGF at higher or lower rates compared to RPE cells from eyes without neovascularization?
Higher
What are the 2 parts of the retinal-blood barrier
- retinal vascular endothelium
- tight junctions between RPE
Photoreceptors are on the ____ side and choriocapillaris are on the _____ side of the RPE
- P= apical
- C=basolateral
What absorbs blue light?
Lutein and zeaxanthin
The driving force to remove water form the apical side
Active transport of Cl- from retina to blood
Where does reisomerization of all-trans-retinol into 11-cis-retinal occur?
RPE
Which growth factor gets involved in choroidal neovasculization?
VEGF
Which disease is due to reduction of epithelia Cl- transport?
A. Retinitis pigmentosa
B. Best’s Vitelliform Macular Degeneration
B
What are 2 characteristics of photoreception
- light detection
- photo absorption
Light detection that lead to vision and depends on photoreceptors (specialized light- sensitive neurons)
Photoreception
Photon absorption by visual pigment that is lying on one of the discs in the outer segment of photoreceptors
Photoreception
Dim light and motion
Peripheral/scotopic
Color and detail
Central/photopic
Scotopic visual system
Rods
Photopic visual system
Cones
Name 4 characteristics of rods
- Not good for detailed vision
- No color vision
- Very sensitive, good for dim vision
- Lower sensitivity to rapidly changing stimuli
Name 4 characteristics of cones
- Specialized for detailed vision
- Specialized for color vision
- Less sensitive
- Higher sensitivity to rapidly changing stimuli
Are there rods in the fovea?
No
Rods comprise ___ of photoreceptors
97%
Rod peak absorption
500-510nm
Does rod convergence increase of decrease sensitivity?
Increases
Where do many rods gather light information on?
Onto one retinal bipolar cell
Are there more rods or cones?
Rods
Are cones more prominent in the fovea or the periphery?
Fovea
What are the 3 different types of cones?
- red (L cones)
- green (M cones)
- blue (S cones)
What is the wavelength of red cones?
560nm
What is the wavelength of green cones?
530nm
What is the wavelength of blue cones?
420nm
What type of cones are not in the fovea?
Blue cones (S)
Doe cones have convergence?
Nope
Are unstable pigments that undergo a chemical change when they absorb light
Photopigments
What makes up photopigments?
Protein (opsin) + chromophore
What makes up rhodopsin?
Opsin + 11-cis-retinal (chromophore)
What pigment is used for vision in dim light?
Rhodopsin
Is rhodopsin soluble or insoluble in water?
Insoluble
T/F: Rhodopsin is more stable and more abundant than cone pigments
True
What are the 3 types of iodopsins?
- erythrolabe
- chlorolabe
- cyanolabe
Photopsin I + 11-cis-retinal absorption max for yellow/red (L-cones)
Erythrolabe
Photopsin II + 11-cis-retinal absorption max for green (M-cones)
Chlorolabe
Photopsin III + 11-cis-retinal absorption max for bluish/violet (S-cones)
Cyanolabe
Is the series of biochemical events that lead from photon capture by a photoreceptor cell to its hyperpolarization and slowing of neurotransmitter release at the synapse
Phototransduction
Is the transformation of light into electrical and chemical signals that produces the perception of light
Phototransduction
What are the steps of phototransduction?
Photoreception–>biochemical cascade–>electronic spread–>slowing of NT release
What is the important channel in the biochemical cascade?
Cyclic-GMP-Gated Cation Channel (CNG channel)
CNG channel allows what 3 things to enter the cell?
- NA+
- K+
- Ca2+
T/F: CNG channel causes the cells to be partially depolarized
True
In the dark, rods have a resting membrane potential of about ___
-50mV
For other neurons, the resting membrane potential of about ____
-70mV
There is net flux of cation outer of inner segment plasma membrane and a net flux of cations into the outer segment plasma membrane, as well as electrical conductance between the inner and outer segment, a complete circuit is made
Dark current
What is the beginning step of biochemical cascade of phtototransduction?
Photoisomerization of rhodopsin
What converts 11-CIS-retinal to all-trans-retinal?
Light
Reduction of all-trans-retinal into all-trans-retinol
occurs in?
Photoreceptors
Reisomerization of all-trans-retinol into 11-cis-retinal
occurs in?
RPE
What is the second step of the biochemical cascade of Phototransduction?
G-protein activation
Metarhodopsin II encounters an _____ G protein
Inactive
What comes to lie over the metarhodopsin II?
The Ga subunit of the G protein
GDP is replaced by___ in the biochemical cascade
GTP
Is it on or off when G protein binds to GTP?
On
Is it on or off when G protein binds to GDP?
Off
When is the G protein active in the biochemical cascade?
When GTP behinds to the Ga subunit
The unit that separates from both Metarhodopsin
and the βγ portion of the G protein
Ga-GTP
What is the 3rd step of biochemical cascade of Phototransduction?
PDE6 activation
What does the activated G protein bind with in the biochemical cascade?
PDE6
The activated PDE6 coverts the ____ into ___
cGMP into GMP
PDE can degrade cGMP by hydrolyzing cGMP into ____
5’-GMP
What is the final step of the biochemical cascade of phototransduction?
Channel closing
What does the reduction of cGMP concentration cause?
CNG channel closure
T/F: Opening of CNG channel put photoreceptors at resting dark-adapted state
True
What are 3 characteristics of electronic spread
- closing of channels
- photocurrent in dark
- photocurrent in light
Closing of channels in the electronic spread reduces the flow of __ and ___ ions into the cell, reducing the dark current and make the membrane potential more ____
Na+ and Ca2+
Make it more negative (hyperpolarized)
Cations moving into the cell (electronic spread)
Photo current in dark
A single photo isomerization closes ion channels and cause a 2% reduction in the photocurrent
Photocurrent in light
Communication of rods with downstream bipolar
cells by the release of ____
Glutamate
Name the 3 characteristics of slowing of NT release
-Communication of rods with downstream bipolar
cells by the release of glutamate
-High level of glutamate release by rods signal total darkness to bipolar cells
-Reduction in the level of glutamate release due to absorption of light
____ level of glutamate release by rods signal
total darkness to bipolar cells
High
What are the 2 factors of phototransduction?
- amplification
- adaptation
Amplification
1 Rhodopsin: _____G proteins
1 Rhodopsin: _____PDE
1 PDE: ___cGMP hydrolysis
100 G proteins
800 PDE
100cGMP
Phototransdution adaptation _____ sensitivity to light, ___ sensitivity in response to bright light, ___ sensitivity in response to dim light, controlled by ___ influx
- Alters sensitivity to light
- Decreases sensitivity in response to bright light
- Increases sensitivity in response to dim light
- Controlled by Ca2+ influx
What photoreceptor sensitivity increases due to convergence?
Rods
What is the key molecule of biochemical cascade to keep CNG channel open?
CGMP
What is the NT between rods and bipolar cells?
Glutamate
List the steps of phototransduction
Photoreception–>biochemical cascade (channel closure)–> electronic spread (cells hyperpolarized)–> slowing glutamate release
a junction between two nerve cells, consisting of a minute gap across which impulses pass by diffusion of a neurotransmitter.
Synapse
An excitatory NT
Glutamate
2 inhibitory NT
GABA and glycine
A change in a cells membrane potential that makes it more negative
Hyperpolarization
Hyperpolarization inhibits APs by ____the stimulus required to move the membrane potential to the AP threshold
Increasing
A change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell.
Depolarization
What 2 cells are light evoked signals transferred onto?
Bipolar and horizontal cells
What cells provide lateral interactions in the outer plexiform layer (OPL)
Horizontal cells
What cells transfer the light signals into the inner plexiform layer (IPL), onto the amacrine and ganglion cells
Bipolar cells
collect the signals ofbipolar and amacrine cells and
transmit these signals to the visual centers of the brain.
Ganglion cells
What type of NT do cone pedicles have?
Glutamate
Is glutamate high or low in darkness?
High
Is glutamate increased or reduced by light?
Reduced by light
What are the 2 different sets of glutamate receptors in cones?
- off cone bipolar cells
- on cone bipolar cells
Are ON cone bipolar cells hyperpolarized or depolarized by light?
Depolarized
Off cone and bipolar cells and horizontal cells are
____ by light
Hyperpolarized
Where do OFF cone bipolar cells transfer signals onto?
Onto OFF ganglion cells
Where do ON cone bipolar cells transfer signals onto?
ON ganglion cells
Where do density of cones, bipolar cells, and ganglion cells increase steeply?
Towards e center of the retina
The optimized visual acuity in central retina requires a ___ cone density and a ____ cone-to-RGC ratio
high cone density and a low cone-to-RGC ratio
One cone connected to a midget bipolar cells connected to a midget ganglion cells
Midget system
Concomitant with the increase in density, the bipolar cells and ganglion cells’ dendritic fields become smaller or larger?
Smaller
What type of NT are in rod spherule?
Glutamate
How many types of rod bipolar cells are there?
One
What is the only rod bipolar cell?
ON bipolar cells
Are ON rod bipolar cells depolarized or hyperpolarized by light?
Depolarized
What is the result of ON center ganglion cells with light on the center of the receptive field only?
Ganglion cell fires rapidly
What is the result of OFF center ganglion cells with light on the center of the receptive field only?
Ganglion cells do not fire
What is the result of ON center ganglion cells with light on the surround only?
Cells do not fire
What is the result of OFF center ganglion cells with light on the surround only?
Cell fires rapidly
What is the result of ON center ganglion cells with no light on the center or surround?
Cells do not fire
What is the result of OFF center ganglion cells with no light on the center or surround?
Cells do not fire
What is the result of ON center ganglion cells with light on the center and surround?
Weak response
What is the result of ON center ganglion cells with light on the center and surround?
Weak response
Modulate the glutamate release by shifts the
activation curves of the cone pedicle Ca2+ channels
Cone horizontal cells
Modulate the glutamate release by shifts the activation curves of the rod spherule Ca2+ channels
Rod horizontal cells
Rod horizontal cells releases ____ providing inhibition of bipolar cell dendrites
GABA
Name the 4 glutamatergic neurons
- rods
- cones
- bipolar cells
- most ganglion cells
Name the 2 GABAergic and glycinergic neurons
- horizontal cells
- most amacrine cells
Name 4 aging changes in the retina
-Nerve fibers within the optic nerve decreases, optic
cup diameter increases
-ILM thickens with age (foveal reflex becomes
dimmer)
-Total # of RPE cells decrease significantly with
age; lipofuscin within RPE cells increases and drusen
increases
-Atrophy increases throughout the retina
An age related retinal atrophy where there is pigmentation in RPE and choroid decreases
Tigroid fundus
An age related atrophy with peripheral RPE degeneration
Reticular degeneration
Which type of cells plays a role in transmitting cones signal to RGC?
Cone bipolar cells
Whay types of cells plays a role in transmitting rod signals to RGC?
Rod bipolar cells and amacrine cells
What change does ON bipolar cells have with light?
Depolarization
What kind of NT do bipolar cells contain?
Glutamate
When the center of RGCs receptive field is exposed to light, which type of RGC is stimulated?
ON-center RGC
Will you have a dimmer foveal reflex when you get older?
Yes
What type of GLUT transporter is insulin dependent and are not found in the retina?
GLUT 4
Hat are the 3 major energy producing metabolic pathways in retinal metabolism?
-Glycolysis
_TCA
-ETC
When is lactic acid produced in the largest quantities?
During sleep or condition that block atmospheric O2 from being absorbed by the eye
What 3 things does ascorbic acid do in terms of protecting the retina and the lens?
- scavengers free radicals
- protects against UV damage
- protects against inflammatory responses
Wen the eye subjected to endotoxins which of the following compounds would protect the eye?
Ascorbic acid
Consider the effect of topical epinephrine to the eye. What effect of metabolism would you expect?
There would be a reduction in oxygen flow due to constriction of vessels
Considering the fact that you dont have vascularization of the lens tissue, what is the primary mechanism for the transport of metabolism for energy in the lens?
Low resistance gap junctions
Name the 2 predominate energy sources for the lens
- HMP shunt
- Anaerobic glycolysis
What does the HMP shunt pathway do in the lens?
- helps sends intermediates in different directions
- produces NADPH
The process involved in maintaining the lens is limited to ____ in order to maintain transparency
Anaerobic respiration of glycolysis
Since the lens is 1/3 proteins, have an energy source that is consistent throughout life is important to have clarity. So what type of energy source do you not want?
One that doesn’t promote oxidation effects (you want to maintain proteins)
What are the 4 functions of the lens?
- refracts light to be focused on the retina
- provides 1/3 of the total dioptric power of the eye (15D)
- allows for accommodation of near objects
- absorbs UV lights and protects the retina from UV damage
The lens is composed mainly of what 2 things?
Water and proteins
The proteins make up ___% of the lens
30-35
What are the percentage of water soluble proteins in the lens?
90%
What type of water soluble/crystalline type is the most prominent?
Alpha (40%)
Produces a phenomenon that contributes to lens
transparency, and gives the lens a significantly higher index of refraction than surrounding fluids
Alpha crystalline
Offers resistance to the degradation of the other
crystalline, beta and gamma, and is called a molecular chaperone
Alpha crystalline
Crystalline concentration varies among the lens, providing a refractive index gradient that is ____in the nucleus, than the outer cortical surface
Higher
Spherical aberration in the lens is _____due to the gradient index system and peripheral flattening
Reduced
Do we want extra water in the lens?
No it will be destructive
Water is pumped out of the lens from the anterior surface by _______
Na+/K+ pump
Water enters the lens from the ____ because of osmotic pressure
Back
Are proteins uniform or un-uniform in the lens?
Uniform
Are proteins small or large in the lens?
Small
Proteins concentration ___ towards the nucleus, and creates a RI gradient that is ____ in the nucleus, than the outer cortical space
Increase and creates a RI gradient that is higher in the nucleus
Where do mitosis of secondary fiber cells occur?
In the germinative zone of anterior lens epithelium
After mitosis, lens fiber cells gradually migrate through the ____ and into the _____ where elongation occurs
Through the transition zone and into the equator
What is the primary protector against oxidative damage in the lens?
Glutathione
Glutathione detoxifies _____
Hydrogen peroxide
Ascorbic acid has a ____ concentration in the lens than the aqueous
Much Higher
Glutathione is transported into the lens from the aqeuous and can be synthesized from ____ cells and ____ cells
Lens epithelial cells and superficial fiber cells
What are 3 forms of cataracts?
- age related nuclear cataract
- age related cortical cataract
- posterior subcapsular cataract
The ability of accommodation____ by one quarter of the age
Decreases
Change in osmolarity causes changes in what 3 things?
- thickness
- radius of curvature
- rx
Unusual changes in rx may indicate _____
Uncontrolled diabetes
What type of proteins does the lens contain the most of?
Crystalline
T/F: the lens absorbs blue light the most to protect the retina
False
Where does Na+/K+ pump located to helping pumping out of water?
Anterior epithelium
What option is the best driving force of water entering the lens from the back?
Osmotic pressure
Which part is responsible for formation of the secondary lens fibers?
Anterior epithelium
What type of changes in the lens are caused by accumulation of sorbitol?
Cataract and rx changes
What are the 5 transparency characteristics of the lens at the cellular level?
- small lens fibers
- uniformity of lens fibers
- regularity of packing
- paucity of organelles
- avascular
In an age related nuclear cataract a decline of ___ makes the fibers susceptible to oxidative damage
Glutathione
When older nuclear fibers lose organelles and their nucleus and gains yellow-brown pigment
Age-related nuclear cataract
In an age related cortical cataract, a decrease in glutathione activity will increase what 3 things?
Ca, Na, and water
A cataract when water forms lake, lakes separate cells, water vacuoles created, cause light scatter, cells burst, proteins exposed, proteins oxidized,
cataracts are formed
Age related cortical cataract
When epithelial-like cells migrate from the equatorial region and accumulate at the posterior pole forming an opacity.
Posterior subcapsular cataract
Do crystalline decrease with age?
Yes!
The lens thickness increases ___ per year
0.22mm
The anterior lens capsule ___ with age, and the posterior lens capsule is ____ with age
ALC increases with age, and the PLC is relatively stable with age
Does the radius of curvature for the anterior and posterior lens increase or decrease with age?
Decreases
The center of the lens moves ___ with age, and the anterior chamber depth ___ with age.
The centers of the lens moves anterior, and the anterior chamber depth decreases with age
Do amino acids decrease with age?
Yes
Is sorbitol hydrophobic or hydrophilic?
Hydrophilic
Glutathione required ___ to reduce free radicals
NADPH
When you have insulin insensitive build-up of blood glucose with an increase in sorbitol production
Diabetic cataract
