Flashcards in Lecture 11 - Retinal phototransduction and signal processing Deck (228):
A relatively spherical and avascular, white dense connective tissue that covers the globe posterior to the cornea.
What does the sclera provide?
a strong tough external framework to protect the delicate optic and neural structures.
The sclera maintains what?
the shape of the globe so that the retinal image is undisturbed and provides attachment for the extraocular muscles to rotate the globe and the ciliary muscle to accommodate the lens.
The window of the eye, it is a mechanically strong and transparent connective tissue that covers anterior 1/6 surface of the eye.
What is the most powerful focusing element of the eye?
Cornea, roughly twice as powerful as the lens.
Specialized epithelial tissue that is responsible for fine-tuning the image that is projected on the retina.
Where is the lens?
Lies inside the eye surrounded by aqueous humor. It is transparent and has high refractive power.
What stabilizes the lens and allow accommodation to occur?
Elastin based zonular fibrils
Uveal tract consists of what three structures
the choroid, the ciliary body and the iris.
What is the Choroid?
Capillary bed nourishing the photoreceptors and outer retina
What are the parts of the Ciliary body?
1) ciliary muscle 2) vascular component
the ciliary muscle does what?
controlling the refractive power of the lens
a vascular component of the ciliary body does what?
that produces the aqueous humor filling the anterior chamber.
Colored portion of the eye seen through the cornea.
What does the iris contain?
two sets of muscles with opposing actions that allow the size of the pupil (opening at the center) to be adjusted by neural control.
Volume behind the cornea and in front of the lens. Filled with aqueous humor.
Region between the vitreous and the lens.
Clear watery liquid that nourishes the cornea and lens. It is produced by the vascular component of the ciliary body.
Thick gelatinous substance filling the space between the back of the lens and the surface of the retina.
Contains neurons that absorb light and process visual information in the images and send that information to the brain.
Oval spot containing a yellowish pigment (xantophyl). Supports high acuity.
Small depression at the center of the macula - has highest spatial acuity.
Whitish circular area where retinal axons leave the eye and travel through the optic nerve to targets in the midbrain and thalamus.
What is the site where blood vessels supply the inner retina enter the eye?
Blood supply for the eye
The ocular vessels are all derived from the ophthalmic artery (OA), a branch of the internal carotid artery.
What are the two distinct vascular systems that supply the eye?
a) the anterior segment (iris and ciliary body) and b) the retinal systems.
Vascularization of the anterior segment
originates from the anterior ciliary arteries and the long posterior ciliary arteries. Penetrating vessels through the sclera vascularize the iris and the ciliary body.
Delivery of metabolic substrates and oxygen to the retina is accomplished by two separate vascular systems
What are the two separate vascular systems of retinal supply?
the inner retinal and choroidal. The retinal and choroidal vessels differ morphologically and functionally from each other.
View with an ophthalmoscope shows what?
the surface of retina and the vasculature of the inner retina
What is cataracts?
Clouding of the lens that affects vision
Most cataracts are related to what?
Cataracts are the leading cause of what?
Cataracts by age 80
more than half of all Americans have a cataract or have had cataract surgery
What are the risk factors for cataracts?
Aging, diabetes, sunlight and smoking
What are the symptoms for cataracts?
Hazy vision, poor night vision, glare and faded colors
What is the treatment for cataracts?
Surgical removal of the cloudy lens and replacement with an artificial lens. Very little recovery time after surgery
What is the process known as cataract formation?
Disruption of the order of the organization of the lens cell fibers or aggregation of the proteins within them can destroy transparency of the cell
Presbyopia causes what?
Loss of lens elasticity with age causes this inability to focus on near objects
Total refractive power =
power emmetropic eye + power of accommodation
What is glaucoma?
Group of diseases that damage the eyeâ€™s optic nerve and can result in vision problems
What are the types of glaucoma?
1) normal tension 2) open angle 3) closed angle
What are the risk factors for glaucoma?
Elevated eye pressure, thin cornea, abnormal optic nerve anatomy, high blood pressure
What is the relationship between intraocular pressure and glaucoma?
Not all subjects with high IOP develop glaucoma
What are the symptoms for glaucoma?
None until its too late, loss of peripheral visual fields
What is the treatment for glaucoma?
Eye drops to decrease aqueous production and/or increase drainage. Surgery.
The circulating aqueous humor does what?
It nourishes the cornea and lens structures that must be transparent and therefore devoid of blood vessels.
Aqueous humor is secreted by what?
the ciliary epithelium lining the ciliary processes
Where does the aqueous humor flow?
around the lens and through the pupil into the anterior chamber
How does the aqueous humor leave the eye?
by passive flow at the anterior chamber angle
What are the risk factors for glaucoma?
High eye pressure resulting from poor drainage of aqueous humor.
Open angle glaucoma:
Slow development of pathology. Caused by obstruction of drainage canals.
Sudden increase in intraocular pressure. Closed or narrow angle between the iris and cornea.
How is intraocular pressure regulated?
At the front of the eye
A â€˜window to the brainâ€™, is part of the Central Nervous System. It is a thin neural tissue (200 microns thick) that lines the back of the eye.
What does incoming light first hit?
the ganglion cell layer, the rest of the inner retina, then the photoreceptor (PR) nuclei and inner segments before the PR outer segments, where phototransduction occurs.
What must light travel through before striking and activating the rods and cones?
the thickness of the retina
Subsequently the absorption of photons by the visual pigment of the photoreceptors does what?
It is translated into first a biochemical message and then into an electrical message that can stimulate all the succeeding neurons of the retina.
How is the retinal message concerning the photic input transmitted?
to the brain by the spiking discharge pattern of the ganglion cells via the optic nerve.
What are the layers of the retina?
3 nuclear (cell somas), 2 plexiform (synaptic connections), 1 nerve fiber layer (NFL).
What are the neuron cell types?
1) photoreceptors 2) horizontal cells 3) bipolar cells 4) amacrine cells 5) ganglion cells
What are the glia cells?
1) Muller glia (radial) 2) microglia
Layers and neuron types:
1) Photoreceptor outer segments (OS), 2) Outer nuclear layer (ONL) 3) Outer plexiform layer (OPL) 4) Inner nuclear layer (INL) 5) Inner plexiform layer (IPL) 6) Ganglion cell layer (GCL) 7) Nerve fiber layer (NFL)
Outer nuclear layer (ONL):
Outer plexiform layer (OPL):
photoreceptor / bipolar /horizontal cell synapses
Inner nuclear layer (INL):
horizontal, bipolar and amacrine cell somas
Inner plexiform layer (IPL):
bipolar/amacrine/ganglion cell synapses
Ganglion cell layer (GCL):
ganglion cell somas
What are Pigmented epithelium (RPE):
melanin-containing cells behind the photoreceptors,
What is the function of pigmented epithelium?
acts as backstop for light, maintains phototransduction machinery of photoreceptors by recycling of PR discs, pigment regeneration and photoreceptor nourishment.
Retinal glia cells
including astrocytes (neurovascular), microglia (immune system) and Mueller (radial glia-like) cells (ionic milieu, guidance during development).
Different subclasses of horizontal, bipolar, amacrine and ganglion cells make distinct contributions to
What is the vertical information flow?
Photoreceptors to bipolar cells to ganglion cells
Lateral information flow is mediated by
horizontal cells and amacrine cells
Cells along the vertical path (photoreceptors, bipolar and ganglion cells) release what?
Cells mediating lateral information transmission (horizontal and amacrine cells) release what?
mostly GABA or glycineric (some exceptions exist..)
What are the two types of photoreceptors for the retina?
Rods and cones
What types of cells are photoreceptors?
they are ciliated cells.
The outer segment of photoreceptors are connected to what?
the inner segment via a connecting cilium.
Outer segment of the photoreceptor
houses the phototransduction machinery
Inner segment of the photoreceptor
housekeeping machinery (nucleus, mitochondria, Golgi apparatus, ER, etc).
Synaptic terminal of the photoreceptor
contacts bipolar and horizontal cells
Neurotransmitter for the photoreceptor
How do photoreceptors respond to light?
With graded hyperpolarizations
In darkness, rods and cones are depolarized near what?
When do photoreceptors fire action potentials?
They donâ€™t, they respond with graded hyperpolarizations
Describe neurotransmitter release when rods and cones are depolarized.
Neurotransmitter is released continuously
How do rods and cones compare to most other neurons?
rods and cones maintain a relatively depolarized membrane potential at rest.
In darkness rods and cones are
depolarized near -40 mV and neurotransmitter (glutamate) is continuously released. When stimulated by light, photoreceptors do not fire action potentials but instead respond with graded hyperpolarizations.
What happens to the photoreceptor hyperpolarization?
it then spreads passively to the synapse where it reduces the release of the neurotransmitter glutamate.
Photoreceptors in the dark
they have a circulating current in the dark
Describe Na+ and Ca2+ cations for Photoreceptors in the dark.
They flow inward through cGMP-gated channels at the outer segment
Describe K+ ions for Photoreceptors in the dark.
They flow outward through potassium-selective channels at the inner segment
Na+ and Ca2+ inflow for Photoreceptors in the dark does what?
depolarizes the cell
K+ outflow for the photoreceptor does what?
acts to hyperpolarize the cell
In the photoreceptor what does the combined action of the depolarIzing and hyperpolarizing ionic currents result in?
a steady, depolarized membrane potential of -40 mV
How do photoreceptors respond to light?
by suppressing the inward cationic current
What does the absorption of light do for the photoreceptor?
it reduces cGMP levels in the outer segment
What is the intracellular transmitter of phototransduction?
What is the effect of the decreased cGMP in the photoreceptors response to light?
1) cGMP-gated channels close reducing the inflow of Na+ and Ca2+ cations 2) K+ ions continue to flow out of the inner segment reducing the amount of positive charge in the cell 3) The photoreceptor becomes hyperpolarized and the amount of neurotransmitter
For the photoreceptors response to light, what does the reduction of inward current result in?
a reduction in intracellular calcium levels.
What are light induced reductions in calcium levels important for?
When does phototransduction begin?
When a pigment molecule absorbs a photon
What is phototransduction?
it is the process by which light is converted into electrical signals.
In pigment activation, disk membranes are packed with what?
the primary light detector, the visual pigment protein rhodopsin (cone opsin in cones).
In pigment activation, what does the pigment consist of?
an opsin molecule that contains the light-absorbing chromophore 11-cis retinal (an aldehyde of vitamin A)
In pigment activation, what are opsins?
They are members of the G-protein coupled receptor (GPCR) superfamily of signal transducing receptors.
What does opsin do?
Opsin tunes the absorption of light to a particular region of the spectrum
What is the effect of absorption of a photon?
it changes the conformation of retinal from 11-cis to all-trans
What does the conformational change induced by the photon lead to?
The conformational change in retinal leads in turn to activation of rhodopsin (R to R* state)
When activated what do opsins catalyze?
the activation of heterotrimeric G-protein known as Transducin
What does active rhodopsin (R*) initiate?
a series of biochemical reactions that lead to a reduction in cGMP levels
What does retinal bind to?
It binds covalently inside a pocket formed by the opsin molecule
What does all-trans retinal do?
it breaks the covalent bond and exits the pocket in the opsin molecule
How is the absorption of a single photon related to amplification?
The absorption of a single photon closes more than 200 channels.
What does the amplification of a single photon lead to?
This leads to a membrane hyperpolarization of ~ 1 mV. Careful observers can see light flashes so dim that only 1 in 100 rods absorb a single photon.
The visual cycle is essential for maintaining the light sensitivity in photoreceptors. It occurs largely in the pigment epithelium.
What is involved in the restoration of retinal?
It gets restored to a form capable of signaling photon capture in a complex process known as the visual (or retinoid) cycle.
In the visual or retinoid cycle, what happens after absorbing a photon?
all trans-retinal dissociates from the opsin and is transported to pigment epithelium.
In the visual or retinoid cycle, what happens after the trans-retinal dissociates from the opsin and is transported to pigment epithelium?
In the pigment epithelium it is re-isomerized and converted back to 11-cis retinal
In the visual or retinoid cycle, what happens to the chromophore 11-cis retinal?
it is transported back to the outer segment where it recombines with opsin to form pigment.
What is dark adaptation?
Restoration of sensitivity after exposure to illumination
In the fovea, what happens to give it higher acuity?
The ganglion cells, IPL, INL are pushed away and are populated by cones while the periphery is populated largely by rods
What does the higher convergence of rods onto rod bipolar cells lead to?
1) high sensitivity 2) low resolution
Midget bipolar cells
1 cone to 1 cone bipolar cell; 1) low sensitivity 2) high resolution
1) Visual angle subtended is 0.5 deg â€“ same as full moon or thumb nail at arm distance 2) Involves ~0.01% of retinal area, but 10-50% of the optic nerve, no S cones, no rods.
1) distributed in periphery â€“ not in fovea 2) very sensitive to light
Which is more sensitive to light, rods or cones?
What is the distribution of rods and cones?
1) Rods = periphery 2) Cones = fovea
Which has the ability to respond to a single photon?
What is required to elicit a response in cones?
About 100 photons are required to elicit a response
What is the relationship between rods and cones to their respective bipolar cells?
1) rods â€“ high convergence onto rod bipolar cells 2) cones â€“ 1:1 (midget bipolar cell)
Describe the sensitivity and spatial resolution for rods and cones?
1) Rods trade off high sensitivity for low spatial resolution 2) cones tradeoff high spatial resolution for low sensitivity
Which mediates high acuity vision â€“ rods or cones?
Which is responsible for color vision â€“ rods or cones?
(rod-only) vision: high sensitivity, low acuity, no color
(cone-only) vision: low sensitivity, high acuity, color
cone and rod acute vision, active together
What is activated in dim light â€“ rod or cone?
What is activated in bright light â€“ rod or cone?
What is retinitis pigmentosa?
A group of genetic eye conditions that leads to incurable blindness, 1:4000 (400,000 in US)
What are the symptoms of retinitis pigmentosa?
1) night blindness 2) tunnel vision 3) usually legally blind by age 40. Loss of ERG.
What is the cause of retinitis pigmentosa?
Mutation of genes for rhodopsin and other rod proteins (PDE, cGMP-gated channels, RDS/peripherin) leading to degeneration of rods and eventually cones. Current count of gene defects exceeds 100
What is the treatment of retinitis pigmentosa?
None. Unclear why the cones die
What is ERG?
The electroretinogram (ERG) provides a measure of retinal function. The ERG is a brief change in potential (<1mV) evoked by a large-field flash of light to the eye and recorded with a contact lenses electrode.
What does the ERG reflect?
â€˜massâ€™ activity of retinal neurons. Valuable tool in diagnosis of retinal pathologies.
What is the leading cause of vision loss?
Age related macular degeneration (AMD) â€“ 10% of people over 50, 33% of people over 75
What is wet AMD?
Abnormal blood vessels behind the retina grow under the macula, leaking and rapidly damaging the retina (choroidal neovascularization)
What is dry AMD?
The retinal pigment epithelium and photoreceptors of the macula degenerate, accumulation of drusen
Which is more common wet or dry AMD?
Dry AMD is 85% of AMD cases
What is drusen?
(dry AMD) yellow deposits â€“ cellular debris
What are the symptoms for AMD?
loss of central vision and acuity
What are the risk factors for AMD?
Aging, smoking, inheritance (local inflammation and the complement system may also be implicated)
What is the treatment for the wet form of AMD?
Proliferation of blood vessels in macula. Treat with laser coagulation of vessels and intravitreal injection of anti-neovascular agents
What is the treatment for the dry form of AMD?
Gradual atrophy of central retina. Antioxidants slow the progression of disease
What is diabetic retinopathy?
Retinal damage from complications of diabetes mellitus
What is the risk for diabetic retinopathy?
Up to 80% of all patients who have had diabetes for 10 years or more
What are the symptoms for diabetic retinopathy?
Early diabetic retinopathy often has no early warning signs. Blurry vision with macular edema. New vessels bleed into the retina and block vision
What is non-proliferative diabetic retinopathy?
Hyperglycemia induced pericyte death leads to incompetence of the vascular walls, microaneurysms and dot and blot hemorrhages. Vascular bleading and cotton wool spots (ischemia)
What is the proliferative stage for diabetic retinopathy?
New, fragile vessels grow, which leak blood
What is the treatment for diabetic retinopathy?
Laser surgery to reduce edema and injections with anti-neovascular factors
in sensory systems most sensory neurons respond best to some form of CONTRAST (differences in stimuli) rather than constant, uniform stimuli.
Contrast though can be of many types:
spatial/luminance, color, spatial/color, motion, depth, optic flow, curvature, differences in face shape, etc.
Receptive field (RF):
That part of sensory stimulus space that, when stimulated, causes a change in the activity of the neuron (stimulus response).
For a visual neuron what would the RF definition mean?
that position in visual space where a change in light (visual stimulus) causes a change in the activity of that visual neuron.
ON center cells
increase their discharge rate to luminance increments in the receptive field center.
OFF center cells
increase their discharge to luminance decrements in the receptive field center.
Receptive fields of ganglion cells have what?
A center and an antagonistic surround
What is the ON center / OFF surround receptive field?
1) Light in the center is excitatory (depolarization) 2) light in surround is inhibitory (hyperpolarization)
What is the optimal excitatory stimulus for the ON center / OFF surround receptive field?
It is a spot of light against a dark background
What is the optimal inhibitory stimulus for the ON center / OFF surround receptive field?
Dark spot against a light background
What is the OFF center / ON surround receptive field?
1) light in the center is inhibitory (hyperpolarization) 2) light in the surround is excitation (depolarization)
What is the optimal excitatory stimulus for the OFF center / ON surround receptive field?
A dark spot against a light background
What is the optimal inhibitory stimulus for the ON center / OFF surround receptive field?
A light spot against a dark background
Neurons whose firing rate is most affected by the edge are where, and ones who are least afffected?
those whose receptive fields lie along the border. Neurons whose receptive fields are completely illuminated are less affected.
Receptive Field in the dim light
spontaneous activity (note that in the text book this condition is referred to as being in the dark, however GCs have very small spontaneous activity in the complete darkness. To be consistent with the firing rates shown in the figure the edge probably tr
Illumination falls on the inhibitory surround
reduction in the discharge rate of the Ganglion Cell
Border of illumination falls on the middle of the Receptive Field
excitatory and inhibitory contributions cancel out â€“ no change in response rate is observed
The center of the Receptive Field is fully illuminated but a portion of the surround remains in the dark area providing only partial inhibition results in what?
strong discharge rate
Where do the functional differences between ON and OFF center GCs arise?
At the synapse between photoreceptors and bipolar cells (BC) in the OPL (outer plexiform layer) the first synapse in the visual system
ON bipolar cells
depolarize in response to light, hyperpolarize in response to dark
OFF bipolar cells
hyperpolarize in response to light, depolarize in the dark
What determines the ON or OFF center properties of the bipolar cells and those of the ganglion cells they innervate?
The glutamate receptors
What leads to increase glutamate release at bipolar cell synapses and depolarization of ganglion cells they contact?
Graded depolarization of bipolar cells
Where does extracting contrast information begin?
at the first synapse in the visual system
How are the center-surround receptive fields constructed?
Antagonistic surround of GC receptive fields is a product of lateral interactions that occur in the OPL by way of horizontal cells (HCs) and in the IPL by way of amacrine cells.
What is responsible for the antagonistic surround of GC receptive fields in the outer plexiform layer?
What is responsible for the antagonistic surround of GC receptive fields in the inner plexiform layer?
Horizontal cell inputs establishes what?
the surround component of the Receptive field of a bipolar cell (and thus that of the ganglion cell to which it is attached).
Cones synapse on what?
On bipolar cells to form RF centers and H-cells to form RF surrounds.
The antagonistic surround inhibit what?
the center response.
Because inhibition spreads laterally from the surround to the center
Input from Horizontal Cells does what?
Opposes changes in the membrane potential of photoreceptors that are induced by phototransduction
Color facilitates what?
Detecting borders of objects, a trichromatic system facilitates distinguishing red and green objects
The three cone types, L, M, S (nominally red, green, blue), are the basis for trichromatic color vision among Old World primates (including humans).
â€¢ Cone opsins:
Like rhodopsin, cone opsins belong to the G-protein coupled receptor (GPCR) superfamily of signal transducing receptors.
Describe the structure of GPCR cone opsins
They have have seven transmembrane domains that traverse the disk membranes in outer segment forming a pocket in which the chromphore resides.
What is the chromophore in the cone opsin?
What does the opsin sequence do?
it tunes the absorption of light to a particular region of the spectrum.
In the opsin sequence, where do significant sequence differences exist?
between Rho and S-opsin and between S-opsin and M-opsin.
M- and L-opsin have
relatively few sequence differences, they have high degree of sequence homology.
The retinal cone mosaic is far from uniform, regular or evenly populated by L, M and S cones. Only 5-10% of cones are S-cones. Interestingly, large differences in the ratio of M and L cone types do not seem to have a severe impact on color perception.
What is the impact on the non uniform distribution of L, M and S cones on color perception?
They do not seem to have a severe impact on color perception
compares activity of three sets of cones with different absorption spectra.
In trichromatic vision the absence of one or more cone classes are responsible for what?
common color blindness: (no L cones: protanope, no M cones: deuteranope, no S: tritanope).
Protanopes and deuteranopes
have difficulty detecting differences between red-and green colors and are the most common of dichromacy affecting 6-8% of males and 0.4% of females (because it is X-linked)
What are the distinct anatomical parallel pathways from the GC to the brain?
1) parvocellular 2) magnocellular 3) koniocellular
Where do the parvocellular and magnocellular pathways originate?
in the P and M ganglion cells
Where do the koniocellular pathway originate?
it originates in small bistratified yellow-blue ganglion cells
M cells (periphery):
1) large receptive fields 2) Good light and contrast sensitivity and temporal resolution (sensitive to motion) 3) not color sensitive 4) large cells - receive input from a relatively large number of photoreceptors 5) Origin of the magnocellular pathway
P cells :
1) small receptive fields (midget cells) 2) provide high acuity and color sensitivity 3) poor light and contrast sensitivity 4) opponent color receptive fields 5) in the fovea a P ganglion cell receives input from a single bipolar cell that receives input
What does a P ganglion cell receive input from?
A single bipolar cell that receives input from a single cone
bi-stratified ganglion cells. Carry short wavelength (blue) information.
What is meant by Color opponent receptive fields:
The outputs of the three cone types are encoded in the retinal circuitry into two color opponent pathways: red vs green and blue vs yellow (green + red).
What is the only way to determine color/wavelength information?
can only be determined through comparisons (i.e. subtractions, differences) between two or more cone types, hence the term â€œopponencyâ€.
P cells of the monkey retina (presumably also of human retina) are known to respond to what?
light with an opponent chromatic organization in their surround.
That is, P ganglion cells of central retina, when recorded from electrophysiologically, have what?
the smallest receptive fields,
How are the P ganglion cells organized?
as red-cone ON or OFF center, and green-cone ON or OFF center.
Each P-ganglion cell type has what?
a larger surround of the opposite polarity and the opponent color.
color opponent ganglion cells
blue ON/ yellow OFF
Intrinsically photosensitive retinal ganglion cells contain what?
Contain primitive opsin
Intrinsically photosensitive retinal ganglion cells response to light.
Autonomous response to bright lights
Intrinsically photosensitive retinal ganglion cells morphology
have vast dendritic trees
What are the roles of intrinsically photosensitive retinal ganglion cells?
1) Papillary control 2) synchronization of circadian rhythms 3) sleep 4) learning
Why is it thought that intrinsically photosensitive retinal ganglion cells play a role in papillary control?
Because they project to the pretectum