Retina and retinal pigment epithelium Flashcards
What layer is the retina in relation to the three coats of the eye?
it is the innermost of the 3 coats
What are the 2 primary layers that the retina consists of?
- Inner neurosensory retina
- Outer simple epithelium: retinal pigment epithelium (RPE)
To what can the 2 primary layers of the retina (inner neurosesory retina and RPE) be traced embryologically?
inner and outer layers of the invaginated optic cup
In adults, what are the 2 primary layers of the retina continuous with anteriorly?
epithelial layers over the ciliary processes and posterior iris surface
What lies between the neural retina and RPE?
a potential space, the subretinal space, across which the two layers must adhere
At what points are the only attachments of the neural retina?
anterior termination the ora serrata, and margins of the optic nerve head
Where does detachment of the retina occur?
between the neural retina and RPE
What does the micrograph show?
the human retina
acronyms:
- NFL = nerve fibre layer
- GCL = ganglion cell layer
- IPL = inner plexiform layer
- INL = inner nuclear layer
- OPL = outer plexiform layer
- ONL = outer nuclear layer
- INS = inner segments
- OS = outer segment
- RPE = retinal pigment epithelium
- CC= choriocapillaries
What happens in retinal detachment?
the neural retina separates from the retinal pigment epithelium (RPE) thus reopening the embryonic intraretinal space or optic ventricle (analogous to ventricles of the brain), known in the adult as the subretinal space
What tends to fill the opened subretinal space in retinal detachment?
proteinaceous exudate
What 3 things normally maintain adhesion of the neural layer and RPE?
- negative pressure
- viscous proteoglycans in the subretinal spce
- electrostatic forces
What binds the retina a) externally and b) on its internal aspect?
- a) externally: Bruch’s membrane
- b) internally: vitreous
What is the relation of the retina to the optic nerve?
the retina is continuous with the optic nerve posteriorly, the site of exit of ganglion cell axons from the eye
What are the 6 key topographical regions of the retina?
- Posterior pole or central retina (area centralis)
- Macula lutea (fovea)
- Fovea centralis (foveola)
- Optic disc
- Peripheral retina
- Ora serrata
What is the posterior pole or central retina known as anatomically?
area centralis
What is the posterior pole or central retina?
5-6mm diameter circular zone of retina situated between the superior and inferior temporal arteries
Which photoreceptors dominate the posterior pole or central retina?
cones
What characterises the posterior pole or central retina histologically?
the presence of more than a single layer of ganglion cell bodies
What is the anatomical term for the macula lutea region of the retina?
fovea
What is the macula lutea?
a 1.5mm diameter area in the posterior pole, 3mm lateral to the optic disc
What colour is the macula lutea and why?
partly yellow
result of xanthophyll carotenoid pigments (zexanthin and lutein) in the cone axons
What may be the purpose of the colour of the macula lutea?
This may serve to act as a short wavelength filter protecting against UV irradiation
What is the anatomical term for the fovea centralis?
foveola
What is the fovea centralis?
central 0.35mm wide zone in the macula, consisting of a depression surrounded by slightly thickened margins
What is the distribution of photoreceptors like in the fovea centralis (foveola)?
cone photoreceptors are concentrated here at maximum density to the exclusion of rods
What is the arrangement of the inner retinal layers in the margins of the pit in the fovea centralis (foveola)?
the inner retinal layers in the margins of the pit are displaced laterally
What is the name of the pit in the fovea centralis (foveola)?
clivus
How does the foveal retina receive nutritional support?
it is avascular, relies wholly on the choriocapillaris
What is the location of the optic disc?
lies 3mm medial to the centre of the macula (fovea)
Why is the optic disc a blind spot?
there are no normal retina layers in this zone as ganglion cell axons from the retina pierce the sclera to enter the optic nerve
What is the diameter of the optic nerve and what happens at its edges?
diameter 1.8mm
slightly raised rim
What is the arrangement of blood vessels at the optic disc?
the central retinal vessels emerge at the centre of the optic disc, pass over the rim, and radiate out to supply the retina
the vein usually lies lateral to the artery
What is the usual relation of the central retinal vein to the artery at the optic disc?
the vein usually lies lateral to the artery
What is the peripheral retina?
the remainder of the retina outside the posterior pole
What is the distance from the optic disc to the ora serrata temporally vs nasally?
- temporally: 23-24mm
- nasally: 18.5mm
What is the thickness of the peripheral retina?
110-140 µm
What are the photoreceptors and neural layers like in the peripheral retina?
rich in rods
only one layer of ganglion cell bodies
What is the ora serrata?
the scalloped or dentate anterior margin of the sensory retina
at this transition zone, the neuroretina is continuous with the columnar non-pigmented epithelial cells of he pars plana
What cells is the neuroretina continuous with at the ora serrata?
the columnar non-pigmented epithelial cells of the pars plana
How does the relation of the ora serrata to the limbus compare temporal side vs nasal side?
the ora serrata is approx. 1mm closer to the limbus on the nasal than on the temporal side
How is the retina divided for descriptive purposes only?
nasal and temporal halves, divided by a vertical line through the fovea
What regions of the retina can the optic nerve head be used to help describe?
used as central point to describe supero- and inferonasal and supero- and inferotemporal quadrants
What is the area of the retina?
1250mm2
What is the range in thickness of the retina?
from 100 μm (periphery) to 230 μm (near the optic nerve head)
What is the retinal pigment epithelium (RPE)?
continuous monolayer of cuboidal/columnar epithelial cells, which extends from the margins of the optic nerve head to the ora serrata where it is continuous with the pigment epithelium of the pars plana
Which type of cells is the RPE composed of?
monolayer of cuboidal/columnar epithelial cells
Between which regions does the retinal pigment epithelium extend?
from the margins of the optic nerve head to the ora serrata
What structure is the RPE continuous with at the ora serrata?
pigment epithelium of the pars plana
What are 6 of the functions of the RPE?
- Maintaining adhesion of the neurosensory retina
- Providing a selectively permeable barrier between the choroid and neurosensory retina
- Phagocytosis of rod and (to a lesser extent) cone outer segments
- Synthesis of the interphotoreceptor matrix
- Absorption of light and reduction of light scatter within the eye, improving image resolution
- Transport + storage of metabolites and vitamins (especially vitamin A)
What is the embryological origin of the RPE?
neuroectoderm
What causes RPE cells to vary in shape and size and what typical pattern of variation do they follow?
vary depending on age and location
more columnar in the central retina (14 μm tall, 10 μm wide) and more flattened (10–14 μm tall, 60 μm wide) in the peripheral retina
What membrane/cells is intimately associated with the photoreceptor outer segments of the RPE?
basal aspect of the cells on Bruch’s membrane and their apical surface
What is the organisation of epithelial cells within the RPE when examined en face?
highly organised hexagonal pattern of homogenously sized cells
What is the number of RPE cells per eye?
varies 4.2 -6.1 million
Label the following on the diagram of the RPE:
- apical microvilli
- lysosomes
- junctional complex and laminal bar
- melanin granules
- lipofuscin
- Golgi apparatus
- basal infoldings
- rough and smooth endoplasmic reticulum
- mitochondria
What are 9 key features of the RPE to be aware of?
- apical microvilli
- lysosomes
- junctional complex and laminal bar
- melanin granules
- lipofuscin
- Golgi apparatus
- basal infoldings
- rough and smooth endoplasmic reticulum
- mitochondria
What is the function of the apical microvilli of the RPE?
aids adhesion, phagocytosis, increased surfaec area of metabolic exchange
What is the function of the lysosomes of the RPE?
contain hydrolytic enzymes which digest photoreceptors
What is the function of the junctional complexes and terminal bars of the RPE?
component of blood-retinal barrier and ensures cell-cell adhesion
What is the function of the phagosomes of the RPE?
contains phagocytosed photoreceptor segments
What is the function of the melanin granules of the RPE?
absorb excess visible light and UV. Reduces free radical damage
What is the function of the lipofuscin of the RPE?
‘ageing pigment’, residual bodies from phagocytic activity
What is the function of the Golgi apparatus of the RPE?
secretion and sulphation of GAGs
What is the function of the basal infoldings of the RPE?
increased absorptive surface
What is the function of the rough + smooth endoplasmic reticulum of the RPE?
protein and lipid synthesis
What is the function of the mitochondria of the RPE?
large numbers indicate active ‘pumping’ epithelium
What do images B and C show?
B = Transmission electron micrograph of human RPE layer.
C = Scanning electron micrograph of the apical surface of the retinal pigment epithelium. Note the hexagonal shape and the ovoid melanin granules, only visible because of post-mortem-induced disruption of the apical cell membrane
CC = choriocapillaries, BM = Bruch’s membrane
To which cells is the RPE fundamental to their function?
photoreceptors
What is the main site of age-related macular degeneration (AMD)?
the RPE layer
What do degenerative changes of the RPE vary with?
the site - periphery v central
What changes happen in the RPE as it becomes atrophic and loses cellularity?
it attempts to cover the defects by enlarging and spreading
What is thought to be the process by which multinuclear cells form in the degenerating RPE?
has been assumed to be a result of cell-cell fusion, similar to process that occurs in other cells e.g. macrophages
however recently thought that failure of cytokinesis may be main mechanism: although nuclei can replicate in the initial stages of cell division and repair, aged RPE cells cannot complete process and cytoplasmic separation of two new cells fails
What substance increases within the RPE with age and what are its properties?
lipofuscin - autofluoreoscent properties
What is the neurosensory retinna?
thin, transparent layer of neural tissue
Wha is the colour of the neurosensory retina in life and why?
red/purple tinge caused by the presence of visual pigments
What is the function of the neurosensory retina?
light stimuli are converted into neural impulses in the retina
impulses are then partially integrated locally before transmission to the brain via the ganglion cell axons in the optic nerve
Which type of cells, among the several cell types of the retina, predominate?
neural cells
In addition to neural cells what are 4 other cells types in the retina?
- glial cells
- vascular endothelium
- pericytes
- microglia
What are the 3 principal neurone cell types that relay impulses generated by light?
- photoreceptors
- bipolar cells
- ganglion cells
What are 3 things which modulate the activity of the principal neurone cell types that relay impulses generated by light in the retina?
- amacine cells
- horizontal cells
- non-neuronal elements
How are the retinal cells organised, as revealed by histological sections?
in a highly organised manner
8 distinct layers including 3 layers of nerve cell bodies and 2 layers of synapses (layers shown in histological section in pic)
What are the 8 layers of the neurosensory retina?
superficial to deep:
- nerve fibre layer
- ganglion cell layer
- inner plexus layer
- inner nuclear layer
- outer plexus layer
- outer nuclear layer
- inner segments
- outer segment
- retinal pigment epithelium
- chorio capillaris
Describe the retinal circuitry as shown in the image
midget ganglion cells and diffuse ganglion cells at the top
synapse onto diffuse bipolar cells, flat midget bipolar cells. Rod bipolar cells and amacrine cells also present here
flat midget bipolar cells and flat midget bipolar cells synapse with cones and rods. horizontal cell axons present here
What are the 2 types of photoreceptor in the human eye?
rods and cones
Where are photoreceptors situated in the retina?
in the outer or ‘sclerad’ aspect of the retina
How many a) rods and b) cones are ther in the human eye?
- a) rods = 115 million
- b) cones = 6.5 million
What is the function of rods? 3 things
sensing contrast, brightness and motion
What is the function of cones? 3 things
subserve fine resolution, spatial resolution and colour vision
How does the density of rods and cones vary in different regions of the retina?
periphery is rod-dominated (30,000/mm2)
cone density increases nearer the macula (150,000/mm2 at the fovea), the fovea being exclusively cones
What is shown in the image?
scanning electron micrograph of human photoreceptors. C = cone
What does the structure of each photoreceptor consist of?
a long, narrow cell wall with an inner and outer segment joined by a connecting stalk consisting of modified cilium
inner and outer segments are separated from the cell body by the outer limiting membrane
outer segments of rods and cones shaped as their name implies (see image)
How do the features of rods and cones relate to the layers of the neurosensory retina?
- nucleus* situated in outer nuclear layer
- axons* pass into outer plexiform layer where they form synaptic terminals (cone pedicle or rod spherule) with bipolar cells and interneurones (horizontal cells)
What are the names of the synaptic terminals formed by rods and cones?
cone pedicle or rod spherule
Which cells do the photoreceptors form synaptic terminals with (at cone pedicle/rod spherule)?
bipolar cells and interneurones (horizontal cells)
What is contained in the outer segments of rods and cones and how are they shaped?
they are shaped as their names imply
contain visual pigments
What is contained in the outer segments of rods and cones?
visual pigments responsible for absorption of light and initiation of the neuroelectrical impulse
How long are rod cells?
100-120 μm
What is the overall shape of rod cells?
long and slender cells
What pigment is contained in the outer segment of rod cells?
rhodopsin
Which light colour/wavelength is rhodopsin sensitive to?
blue-green light (maximal spectral sensitivity 496nm)
What type of conditions are rod photoreecptors uesd for?
vision in dark-dim conditions
Where within rod photoreceptors is rhodopsin contained?
within the membrane-bound lamellae or discs (up to 1000 per cell, 10-15nm thick), that are enclosed by a single cell membrane (a conceptually useful analogy is to liken them to coins stacked inside a stocking)
What is the width of each outer segment of rod photoreceptors? What is the length?
width: 1-1.5 μm
length: 25 μm
Within which part of rod photoreceptors are the membrane-bound lamellae or discs produced?
From here, where do they travel?
at the base of the outer segment (the ciliary connection)
from here, travel to the tips over the course of 10 days, which are enclosed by the apical microvilli of the RPE
What is the relationship between the apical microvilli of the RPE and the tips of the rod photoreceptors?
the apical microvilli enclose the rod tips; they are phagocytosed by the RPE cells in a circadian manner (predominantly shed in the early morning)
What substance separates the rods from each other?
a modified extracellular ground substances known as interphotoreceptor matrix
What key type of protein is present in the interphotoreceptor matrix between rods?
135kDa glycoprotein, called interphotoreceptor binding protein (IRBP)
What are the inner and outer halves of the inner segment of the rods known as?
- inner half: myoid
- outer half: ellipsoid
What connects the ellipsoid (outer half of the inner segment) of rods to the outer segment?
a modified cilium (nine doublet microtubules without a central pair) whose basal body is situated in the ellipsoid
What is the structure of the cilium, which connects the outer half of the inner segment of rods (ellipsoid) to the outer segment?
nine doublet microtubules without a central pair
What does the cilium (in rod photoreceptors) represent embryologically?
the embryological vestige of the ciliated neuroepithleial cells that line the primitive retinal or optic ventricle
What is the functional role of the cilium in rod cells?
acts a a conduit for metabolites and lipids between the inner and outer segments
What is contained in the ellipsoid (outer half of the inner segment of rods) and what does this indicate?
numerous mitochondria (indicative of high metabolic activity)
What structures are present in the myoid, the inner half of the inner segment of the rods? What do they indicate?
- Golgi apparatus
- smooth endoplasmic reticulum
- microtubules
- glycogen
metabolically and sytnhetically active cell
How many spectrally distinct cone types exist in most diurnal animals, and what is the role of each?
2 spectrally distinct types:
- one maximally sensitive to short wavelengths
- one maxillay sensitive to long wavelengths
= dichromatic retina
What is the term given to a retina consisting of two spectrally distinct cone times?
dichromatic retina
How many types of cones exist in humans, Old world primates, and apes?
3 - trichromatic retina
What are the 3 types of cones present in humans generally referred to as?
blue green and red (or short, medium and long wavelenth) sensitive cones
How does the length of cone outer segments compare to rods?
they are generally shorter than rods and generally conical (6 μm at the base, 1.5 μm at the tip)
What is the arrangement of cones in the fovea?
they are long, slender and tightly packed
How does the way that lamellae (or discs) are arranged in cones differ from that in rods?
in cones, the lamellae are not surrounded by plasma membrane in the same manner but are in free communication with a interphotoreceptor space
What are 3 ways in which the lifespan of cone discs differs from rods?
- cone discs have a greater lifespan than rods
- cone discs are not produced in the same manner as rods
- cone discs do not undergo circadian phagocytosis by the RPE cells
What structures surround cone discs?
the long villous melanin-containing apical processes of the RPE
What is the approximate length of cones?
60-75 μm
How is the outer segment in cones connected to the ellipsoid region?
cilium (similar to rods)
What organelle is high in number in cone ellipsoid regions?
mitochondria - around 600 mitchondria per cell
How can the cell body of the cone be easily identified histologically, and where is it located in terms of layers of the retina?
due to large pale-staining nucleus and perinuclear cytoplasm
located in the sclerad aspect of the outer nuclear layer
What connects the cell bodies of rods and cones to their synaptic terminals?
an inner fibre
What are the respective names of rods’ and cones’ specialised exanded synaptic terminals?
rods: spherules
cones: pedicles
What do the specialised synaptic terminals, spherules and pedicles, of photoreceptors, synapse with?
bipolar and horizontal cells
What is contained in the spherules and pedicles of photoreceptors?
many highly specialised presynaptic vesicles
How does the location of rod spherules differ from cone pedicles?
rod spherules lie more sclerad than cone pedicles
How does the relations of rod spherules & the bipolar and horizontal cell processes differ from that of cone pedicles? What is this called?
rod spherules are more deeply indented by bipolar and horizontal cell processes (telodendria)
What specialised region is present between two adjacent nerve fibres?
synaptic ribbon
What is the horizontal cell telodendria with the rod cell spherule like compared with the bipolar telodendria?
The horizontal cell telodendria penetrate deeply into the spherule; the bipolar cell dendrites (from one to four cells) have a shallower penetration
How many processes from horizontal and bipolar cells may by embedded in one rod cell spherule?
up to 5 processes
Are there connections between rod spherules / cone pedicles?
no contact between rod spherules
but cone pedicles may be connected by gap junctions
How does the width of cone pedicles compare with rod spherules and what is the shape?
cone pedicles are broader (7-8 μm) and have a pyramidal shape
What is the structure of cone pedicles?
- there are up to 12 indentations, each of which contains three neruonal terminals (triad)
- the central process in each triad is a midget bipolar cell dendrite (each may have multiple contacts with the same pedicle)
- the laterally disposed processes in the triad are horizontal cell processes that may also be involved in several triads on the one pedicle
What is the central process in each triad of each cone pedicle indentation? What are the laterally disposed processes?
central: a midget bipolar cell dendrite
laterally: horizontal cell processes
Up to how many synaptic ribbons may there be in each pedicle?
up to 25
How many horizontal cells is each cone usually contacted by?
4-6 (all the horizontal cells in the immediate area of field)
What is also present on each cone pedicle (as well as midget bipolar cell and horizontal cells processes)?
numerous shallow indentations or synapses with flat diffuse bipolar cells
Which retinal layer does the nerve fibre layer of Henle in the fovea correspond to?
outer plexiform layer
