Retina (Q3) Flashcards
What does the posterior pole include?
Area of retina bordered by the superior and inferior temporal vasculature and includes the macula and optic nerve head. It is the area evaluated when performing direct ophthalmoscopy
How many microns is a third of a disc diameter? ~0.33 DD = _____
500 microns (know for 2nd year)
What is the range of average optic disc diameters in mm?
1.5mm - 2.2mm
What are the parts of the macula from largest to smallest/outer to inner?
Macula, perifovea, parafovea, fovea, foveola
Which cells are in high number in the parafovea?
Bipolar and ganglion cells
Which part of the macula is ONLY cones?
Foveola
What is the average diameter of the retina from ora to ora?
32mm
Where does the Foveal Avascular Zone receive blood since it is devoid of retinal vessels?
From the choroid
What are the three possible blood supplies to the retina?
Choroid (supplies outer 1/3), central retinal artery (supplies the inner 2/3), and cilioretinal artery (to macular area, seen in 20% of the population)
What are the 10 layers of the retina?
- RPE 2. Photoreceptors 3. External limiting membrane 4. Outer nuclear layer 5. Outer plexiform layer 6. Inner nuclear layer 7. Inner plexiform layer 8. Ganglion cell layer 9. Nerve fiber layer 10. Internal limiting membrane
Which are the first-order neurons in the retina?
Photoreceptors
Which are the second-order neurons in the retina?
Bipolar cells
Which are the third-order neurons in the retina?
Ganglion cells
About how many photoreceptors, bipolar, and ganglion cells are there (each)?
100 million photoreceptors, 36 million bipolar cells, 1 million ganglion cells (retinal pathway is an example of a converging system)
About how many photoreceptors can an RPE cell support?
Each RPE cell interacts with 30-40 photoreceptors
Which of rods or cones are responsible for scotopic and which is responsible for photopic vision?
Rods for scotopic (night vision), cones responsible for photopic (daytime vision)
What is the name of the structure that connects the outer and inner segments of a photoreceptor cell?
Cilium
What are the two regions in the inner segment of a photoreceptor cell?
Myoid and Ellipsoid
What cellular organelles are found in the myoid region of the photoreceptor?
contains ER and Golgi apparatus for protein synthesis
What cellular organelles are found in the ellipsoid region of the photoreceptor?
Contains mitochondria, important for energy for the cell
What are the synaptic terminals of the photoreceptors called for rods, and for cones?
Rods = spherules
Cones = pedicles
What happens to old outer segment discs of the photoreceptor?
Discs are shed throughout the day and phagocytosed by the lysosomes in the RPE cells
About how many millions of cones are there?
4-5 million!
Which type of cone is found less but more consistent in ratio to the other two? S, M, or L?
S, short-wave, blue cones are fewer but have a more constant ratio to the other than M and L to each other have
About how many millions of rods are there?
80-100 million!
Where is the density of rods the greatest?
3mm away from the center of the fovea (rod ring)
Where is the density of cones the greatest?
fovea
Where are photopigments produced and what are the 2 components?
Produced in the inner segment of the photoreceptor, composed of chromophore and opsin
What is the photopigment in rods called?
Rhodopsin
What is the difference between chromophore and opsin?
Chromophore absorbs light and begins process of phototransduction, opsins are responsible for wavelength sensitivity/absorption characteristics and are different for each type of cone
How common are colour deficiencies (what percent of population)?
4.5% of the population has a colour deficiency, most are genetic
Which chromosomes are the genes that code for human opsin found?
The genes for M and L cones are located on the X-chromosome, the genes for S cone are on chromosome 7 and the Rhodopsin genes are located on chromosome 3
Which cone genes developed alongside each other?
M and L cone genes are 98% homogenous. Homology to S cone is only 40% suggesting that the S cone evolved at a different time
What is CHRPE?
Congenital hypertrophy of the RPE, caused by enlarged RPE cells with densely packed melanin granules, can be associated with colon cancer
What are the symptoms of cone dystrophy?
photophobia, difficulty distinguishing colours
Where is the external limiting membrane and what is its function?
Not a true membrane, it is formed between Muller cells and photoreceptors at the level between photoreceptor inner segments and cell bodies. Functions to restrict the movement of large molecules (has zonula adherens)
What are the two synaptic layers of the retina?
Outer plexiform layer and inner plexiform layer
What is the neurotransmitter released from the photoreceptors’ synaptic terminals?
Glutamate
What is the “middle limiting membrane” of the retina?
the OPL, marks the extent of the retinal vasculature, choroid for outer and CRA for inner retina
What are the two capillary networks in the retina and which layers are they found in?
Deep - located in the inner nuclear layer
Superficial - located in the nerve fiber layer
What are exudates and where are they found?
lipid material that leaks from blood vessels, found in the OPL, associated with hypertension, diabetes, hereditary ocular conditions, wet AMD. different from drusen!
What is retinoschisis and where does it occur?
splitting of the retina at the level of the OPL (not an RD)
What cell bodies are found in the inner nuclear layer?
cell bodies of horizontal, bipolar, amacrine, interplexiform, and Muller cells
(also is the location of the deep capillary network)
Which layers of the retina are dot and blot hemorrhages located in?
In the OPL or INL, often associated with uncontrolled diabetes or hypertension, resolve over several months
What is the function of horizontal cells?
single axon and multiple dendrites to carry information horizontally across the retina, synapsing with photoreceptors, bipolar cells, or other horizontal cells in the OPL
What is the physiology of the synapses from horizontal cells?
Depolarize in the dark, provide inhibitory feedback to photoreceptors and inhibitory feed-forward to bipolar cells, “lateral inhibition”, NTs are glutamate or GABA
What is the function of bipolar cells?
To transmit information from the photoreceptors to the ganglion cells (done with graded potentials)
How many types of bipolar cells are there and how do they differ?
11 types, depends on size, synaptic connection and communication. However, they all have the same function, NT (glutamate), and receptive fields (either ON or OFF)
What is the difference between diffuse and midget bipolar cells?
based on the extent of the dendrites, diffuse has a wide range of influence contacting multiple cones (5 in center, 10-15 in periphery) and converges information, midget has a small range of influence contacting only a single cone in the fovea or 2-3 cones in the periphery.
What is the difference between flat and invaginating bipolar cells?
based on the dendrites placement on the cone pedicle, flat are superficial contact while invaginating are located within the cone pedicle
What are the characteristics of the rod bipolar cells?
the ONLY bipolar cells that contact rods, not found in the foveola, rarely synapse directly with ganglion cells (will synapse with amacrine cells), a single rod bipolar cell can contact 15-20 rods in central retina or up to 80 rods in the peripheral retina
How are blue cone bipolar cells different?
connect widely spaced blue cones rather than neighboring cones
Which classification type of bipolar cell depolarizes in the light and which depolarizes in the dark?
ON-cells depolarize in the light
OFF-cells depolarize in the dark
Which cell in the retina carries information both vertically and horizontally, and also produces action potentials?
Amacrine cells
How many kinds of amacrine cells are there, including stratified and diffuse? (not asking groups)
30-40 kinds
The most well known amacrine cell is AII, where does it synapse?
AII is found in the rod pathway connecting rod bipolar cells (synapse with up to 80) to ganglion cells
Which neurotransmitters are released by amacrine cells?
GABA and glycine (amacrine cells are inhibitory, feedback to bipolar cells and inhibitory feed-forward to ganglion cells)
What is known about the interplexiform cells?
have large cells bodies in the INL with processes in the OPL and IPL, relaying information laterally
How thick is the ganglion cell layer?
1-2 cells thick in the retina, with 4-7 cell layers thick in the macula, (less near the ora serrata)
Approximately 18 different kinds of ganglion cells fall into one of two broad categories:
-Parvocellular (P-cells)
-Magnocellular (M-cells/parasol ganglion cells)
Which layers of the LGN do P-cells vs. M-cells project information to?
P-cells project to layers 3,4,5,6
M-cells project to layer 1,2
Which types of information are the P-cells vs. the M-cells sensitive to?
P-cells are sensitive to colour and fine detail (‘what’ pathway)
M-cells are sensitive to dim changes in illumination and motion (‘where’ pathway) broader information
What are the two types of P-cells?
- P1 ganglion (midget) cells, most common, only synapses with 1 midget bipolar cell which only goes to 1 cone
- P2 ganglion cells are larger and synapse with multiple bipolar cells
Do ganglion cells produce action potentials or graded potentials?
Action potentials!
Where is the nerve fiber layer the thickest and where is it not present?
NFL is thickest near the ONH and not present in the fovea
Which capillary network are flame-shaped hemorrhages associated with and which layer of the retina is this network found in?
Superficial capillary network found in the nerve fiber layer
What layer and what disease/conditions are flame-shaped hemorrhages associated with?
in the NFL, associated with hypertension, vein occlusions, etc.
What is a wedge defect?
A focal loss of ganglion cell axons, appearing narrower near the disc and broader moving away. associated with glaucoma, and best visualized with a red-free filter
What are cotton wool spots?
Fluffy, white patches located in the NFL due to areas of infarction, caused or associated with diabetes, hypertension, etc.
What is the innermost layer of the retina and what is it composed of?
Internal limiting membrane, it is composed of the footplates (‘ends’) of Muller cells and is continuous with the internal limiting membrane of the ciliary body
What are the most common and largest glial cells in the retina?
Muller cells, with cell bodies in INL and extending from ELM to ILM
What are the functions of Muller cells in the retina?
About 10 million, fill gaps, provide structure, regulates K+ ions, maintain extracellular pH, recycles NTs, metabolizes, synthesizes and stores glycogen
What is retinal sheen?
Reflection of the ILM seen with ophthalmoscopy, glistening reflection seen in younger patients
What is an epiretinal membrane?
(ERM or macular pucker) in middle-age to elderly patients, it is a translucent, white/gray membrane composed from a proliferation of Muller glial cells, causing reduced acuity and distortions.
Membrane can be seen on OCT (thickened area) and show striations in fundus photos
What are some differences to the layers of the eye at the macular region?
Macula lutea appears as a dark region in central retina, RPE cells are taller and contain more pigment, choriocapillaris is thickest at the macula (no capillaries located in the fovea, FAZ)
no GCL, NFL over macula, etc.
What are the pigments in the macula that give it a yellow hue?
lutein and zeaxanthin
Which of the original 10 layers of the retina are present in the foveola?
RPE, photoreceptors (only cones), external limiting membrane, outer nuclear layer, Henle’s fiber layer (same as OPL), and internal limiting membrane
What is the purpose of the pigments lutein and zeaxanthin?
found in the inner segments of photoreceptors, reduce chromatic aberration and protect against free radicals and UV light
(possibly associated with macular degeneration)
What is the foveal light reflex?
light at the fovea seen in a young, healthy fovea. goes away with age as the ILM thickens
What are the risk factor for macular degeneration?
age, race, family history, UV exposure, tobacco use
What are the two classification of AMD?
Dry AMD (associated with drusen and AREDS2 vitamins) and Wet AMD (associated with vascular leakage and anti-VEGF injections! yay)
Subretinal fluid (SRF) is found between which layers of the retina? What about intraretinal fluid (IRF)?
SRF is between RPE and photoreceptors, IRF is within the retina.
There also can be sub-RPE fluid below RPE
What might be the cause of a macular hole?
vitreal traction, trauma, or idiopathic, etc.
What might cause cystoid macular edema (CME)?
post-op (cat sx.), vein occlusions, etc; edema due to poor fluid balance by Muller cells
What are the four zones of the peripheral retina?
Near periphery is the 1.5mm ring adjacent to the macula, Middle periphery is the next 1.5mm ring,
Far periphery is 9-10mm temporally+16mm nasally
Ora serrate is 2.1mm temporally and 0.7mm nasally
Describe the appearance of the peripheral termination of the retina
has a scalloped, pigmented appearance, composed of dentate processes and oral bays
Where are the long posterior ciliary nerves typically seen?
usually nasally and temporally (3- and 9-o’clock positions)
What are the possible symptoms of a retinal hole/tear?
new flashes of light and changes in floaters but often asymptomatic
What is lattice degeneration?
Common atrophic finding of the peripheral retina, oval or linear patches of retinal thinning, can have holes within. Associated with (high) myopia
What pathology is associated with having a “curtain” in vision?
Retinal detachment
What is cobblestone (pavingstone) degeneration?
well-defined, yellow/white patches between the equator and the ora serrata, no retina or RPE and so the underlying sclera and choroid is seen. it is a benign and incidental finding
What is reticular (honeycomb) degeneration?
common pigmentary finding in the periphery of older patients, characterized by a fine network of pigment. incidental and no clinical significance
What is the primary source of energy for the retina?
Glucose via facilitated diffusion from choriocapillaris, generates energy through glycolysis (aerobic and anaerobic, retinal oxygen consumption is high) and stored in the Muller cells
What is the Blood Retinal Barrier?
Tight junctions between RPE cells make a physiological barrier with the choriocapillaris and retinal capillaries, regulating ions, molecules, water flux, and waste into and out of the retina
What are the functions of the RPE?
Ion balance and transport, phagocytosis of photoreceptor discs, vitamin A storage, secretion of VEGF and PEDF, absorbs excess scattered light and overall support cells for photoreceptors, also creates a blood-retinal barrier
T/F: RPE cells are the most active phagocytic cells in the human body
True, their lysosomes ingest up to 2000 discs per day (rods in the morning, cones in the evening)
What happens to lactate in the retina?
Lactate is the byproduct of anaerobic metabolism, affect pH and has to be moved out through the RPE
What are some diseases associated with lipofuscin?
Best’s disease (usually in young patients), adult vitelliform dystrophy (may look like AMD on fundus photo), choroidal melanoma (lipofuscin can be a metabolic signal of cancer), and Stargardt’s disease (young patients, low VA)
What is the significance of Vitamin A in the retina?
Vitamin A diffuses through the large fenestrations of the choriocapillaris to the RPE cells that store and metabolize(oxidize) them. Vit A is necessary for the transduction cascade function as 11-cis retinal
What is the purpose of VEGF?
RPE releases VEGF into the choroid to maintain the choriocapillaris.. if secreted into the retina can cause neovascularization :( (ex. in PDR or AMD)
What is the purpose of PEDF?
compliment to VEGF, an inhibitor of neovascularization
What is mesopic vision?
in between light settings, occurs during twilight or transitional light, mixed colour perception (both rods and cones)
What is phototransduction?
turning photons into an electrical/neural signal and to be transmitted to the brain
Where does the phototransduction cascade take place?
the outer segment of photoreceptors
What is opsin?
A G-protein coupled receptor, membrane protein composed of different amino acids that determine which wavelengths to absorb
What is a chromophore?
A molecule that absorbs the photon, derivative of Vitamin A, the photon turns 11-cis retinal to all-trans retinal
What is rhodopsin?
Composed of opsin and 11-cis retinal, located on the outer segments of rods within the disc membranes, absorbs photons maximally at 507nm
What wavelength will a cyanolabe cone photopigment absorb maximally?
420nm (short)
What wavelength will a chlorolabe cone photopigment absorb maximally?
531nm (medium)
What wavelength will an erytholabe cone photopigment absorb maximally?
588nm (long)
What does the photoreceptor do in the dark?
Depolarize, releases glutamate due to Na+ circulation, membrane potential is -40mV, voltage-gated Ca2+ channels are open
How does Na+ circulate in the photoreceptor? (dark)
Inner segment: Na+ out/K+ in via Na+/K+ ATPase pump
Outer segment: Na+ enters through ligand-gated ion channels (ligand is cGMP)
Which cells release glutamate?
Photoreceptors, bipolar cells, ganglion cells
Which cells release GABA and glycine?
Horizontal cells and amacrine cells
What is a ribbon synapse?
Protein complex that facilitates the constant release of NT into the synaptic cleft, found in photoreceptors and bipolar cells
What happens to the Na+ circulation in the photoreceptor during the light response?
cGMP decreases, resulting in the closure of ligand-gated Na+ channels, sodium will continue to be pumped out of the inner segment but can’t circulate back, resulting in hyperpolarization, closing Ca2+ channels, and the slowing or stopping of NT release.
Which bipolar cells (ON or OFF) invaginate on the pedicles and which have a flat placement?
ON-bipolar cells invaginate, OFF-bipolar cell are flat on the pedicles of a cone
If any part of the surround of an ON-center, OFF-surround bipolar cell receptive field is stimulated, the signal will be an _____ message.
an OFF message
If the center of an ON-center, OFF-surround cell is stimulated, it sends an ____ message.
an ON message
If the center of an OFF-center, ON-surround cell is stimulated, it sends an _____ message.
an OFF message
If any part of the surround of an OFF-center, ON-surround bipolar cell receptive field is stimulated, the signal will be an ______ message.
an ON message
What is receptive field?
an area of the retina that, when stimulated, elicits a response in a retinal neuron
(present in bipolar and ganglion cells, as well as the LGN and striate cortex)
Which bipolar cells depolarize in the dark?
OFF-bipolar cells depolarize in the dark
Which bipolar cells depolarize in the light?
ON-bipolar cells
Which bipolar cells hyperpolarize in the dark?
ON-bipolar cells hyperpolarize in the dark
Which bipolar cells hyperpolarize in the light?
OFF-bipolar cells hyperpolarize in the light
Generally, when there is depolarization is there more or less glutamate being released?
More glutamate released
Generally, when there is hyperpolarization is there more or less glutamate being released?
Less glutamate released
Do photoreceptors depolarize or hyperpolarize in light and do they release glutamate in this condition?
Photoreceptors hyperpolarize in the light and stop releasing glutamate
Do photoreceptors depolarize or hyperpolarize in the dark and do they release glutamate in this condition?
Photoreceptors depolarize in the dark and release glutamate
Which receptor does the OFF-bipolar cell have?
Ionotropic receptor
Which receptor does the ON-bipolar cell have?
Metabotropic receptor
All rod bipolar cells are ____-cells
ON-cells
What type of amacrine cells do rod bipolar cells synapse with?
AII amacrine cells
All photoreceptors are considered ____-cells
OFF-cells
What does the ON/OFF categorization of retinal cells describe?
ON or OFF based on the light condition when the cell depolarizes, these cells provide two information processing channels for differentiating light and dark signals
Do rods or cones have faster kinetics?
Cones (however they are less sensitive and difficult to saturate)
What is the renewal system?
the system describing how all-trans-retinal reduces to all-trans-retinol, and then carried to the RPE where it is converted back to 11-cis-retinal to be recycled and go back to photoreceptors for phototransduction again
Which type of ganglion cell is sensitive to rapid movements?
M-cells (Magnocellular, “parasol” ganglion cells)
What is the most common type of ganglion cell?
80% of ganglion cells are P1 cells (midget ganglion cells)
Which type of ganglion cell is associated with cones?
P-cells (Parvocellular)
What are the differences in responses and transmission for P-cells and M-cells?
P-cells have a more sustained response and slower transmission
M-cells have a more transient response and faster transmission
T/F: ON-center midget ganglion cells (P1) only synapse with ON-center midget bipolar cells
True, like cells synapse with other like cells (diffuse bipolar cells synapse with ganglion cells of the same ON and OFF tendencies
What part of the receptive field of the ganglion cell can be stimulated to give more APs?
A larger stimulus size in the excitatory center of the ganglion cell
What are the 3 types of horizontal cells?
HI - primarily contact M- and L-cones
HII - primarily contact S-cones
HIII - large dendritic tree that synapse with many cones
Do amacrine cells depolarize in the light or dark?
depolarize in the light
What are the four groups of amacrine cells? besides being classified as stratified or diffuse
narrow field, small field, medium field, and large field
AII amacrine cells connect to rod bipolar ON-cells and send information where?
To ON- and OFF-ganglion cells via gap junctions (releases glycine)
Which of the four groups of amacrine cells do the AII cells fall into?
narrow-field
Which of the four groups of amacrine cells do A17 cells fall into and what is their action?
wide-field group, appear to modify signals from rod bipolar cells to AII cells
Which of the four groups of amacrine cells do A18 cells fall into and what is their action?
wide-field group, possible role in regulating scotopic vision, releases DOPAMINE!
What are the functions of Muller cells?
Main function is the regulation of fluid balance! (water balance regulated by K+), also does some recycling of all-trans-retinal (majority is done by the RPE)
What are some changes to the retina due to aging?
loss of around 5000 ganglion cells per year
RPE cells decline, decrease in lysosomal activity and can begin to have drusen
hypertrophy of Muller cells
peripheral retinal changes (pavingstone/cobblestone degeneration and reticular degeneration)
How many minutes does it take the eye to recover its sensitivity in the dark after being exposed to bright/prolonged light?
20-30 minutes
How many minutes does it take the eye to recover its sensitivity to bright light after being in the dark?
5-10 minutes (cones are less sensitive than rods, so takes less time to recover)
What molecules control light/dark adaptation?
Ca2+ and cGMP, regulate NT release
What factors can affect dark adaptation?
the intensity and duration of pre-adapting light –the greater the intensity or the greater the duration of light exposure, the longer it takes for dark adaptation
also affected by the position of the retina, wavelength distribution of light used, and rhodopsin regeneration
If only the fovea is stimulated during exposure to light will the dark adaptation take longer or shorter than if an area of both rods and cones are stimulated?
if only fovea is stimulated the dark adaptation will be slower
How does the wavelength of the light affect a dark adaptation?
the rod/cone break of the dark adaptation graph happens fastest with violet light and is not seen with longer wavelength such as red, so red doesn’t cause a slowed dark adaption like the other colours would
What is rod monochromacy (aka: achromatopsia)?
partial or complete inability to see colours, rod photoreceptors are used in all lighting conditions, but scotopic conditions are still the best in these cases (debilitating glare in the light, can use red filters to help)
How does rhodopsin regeneration affect dark adaptation?
recovery from light requires efficient inactivation of transducin and PDE to reverse the cascade, reactivate rhodopsin and restore cGMP, so that the photoreceptor can respond to the next photons.
this is considered a rate-limiting step
BRB protects the retina to some extent but some drugs can still cross, which drugs are known to alter the NTs released?
Glutamate can be affected by riluzole (for ALS), phencyclidine, or ketamine
GABA can be affected by depressant drugs, and marijuana
Glycine can be affected by schizophrenia medications
Where is the rod ring?
rod density is greatest about 5mm (20 degrees) concentrically from the fovea in an area known as the rod ring
What are the 3 different photopigments (iodopsins) in the cones?
Cyanolabe (blue): maximally absorbs photons at 426nm
Chlorolabe (green): maximally absorb photons at 530nm
Erythrolabe (red): maximally absorbs photons at 557nm
How does the ILM differ at the optic disc from the rest of the retina?
at the optic disc the ILM is formed by astrocytes, and in the rest of the retina the ILM is formed by Muller cells
