Retina and RPE part 3 Flashcards
What are 3 key types of retinal neuroglia?
- Astrocytes
- Müller cells
- Microglia
What is the principal and predominant glial cell in the retina?
Müller cells
Which central nervous system cells are Müller cells analogous to?
oligodendrocytes
Within which 3 retinal layers are astrocytes predominantly found in, and what is their outer limit?
3 layers:
- Nerve fibre layer
- Ganglion cell layer
- Inner plexiform layer (site of cell bodies)
Outer limit: vitread aspect of the inner nuclear layer in humans
What is the structural arrangement of astrocytes?
they form an irregualr honeycomb scaffold beween vessels and neurones perpendicular to the Müller cells
What are the 2 shapes that astrocytes may appear as?
- fibrous (elongated)
- protoplasmic (rounded)
What structures are contained within astrocytes and what are these structures made of?
abundant cytoplasmic structural fibrils (10nm in diameter) consisting of glial fibrillary acid protein (GFAP)
In which parts of the astrocyte cells is there a high concentration of expression of GFAP (glial fibrillary acid protein)?
where the cells are stressed
How are astrocytes often oriented?
perpendicular to the direction of the neurone cell bodies or processes, such as in the nerve fibre layer
What may be the role of atrocytes?
isolate the receptive surfaes of neurones int eh retina thus preventing unwanted signals or effects in neighbouring neurones
What substance is abundant in the cytoplasms of astrocytes?
glycogen
What connections due astrocytes form with neighbouring astrocytes?
gap junctions
What is shown in the image?
scanning electron micrograph of astrocytes surrounding nerve fibre bundles in the inner retina
What is shown in the image?
relations of astrocytes shown with antibody to glial acidic fibrillary protein (GFAP) red and lectin-stained vessels (pale gree)
How are astrocytes related to damage in the retina?
when injured, the retina frequently responds by forming astroglial scars
normal age-related degenerative processes in the peripheral retina (microcystoid degeneration) are accompanied by astrocyte proliferation
What can disruption of the inner limiting membrane of the retina result in (in relation to astrocytes)?
astrocyte prolifeation in the subhyaloid spaec and in the vitreous itself
What are Müller cells?
the principal supporting glial cells of the retina
Which cells are Müller cells considered analogous with in the CNS?
radial glial or ependymal cells
What is the orientation of Müller cells in the retina?
radial orientation
What do Müller cells extend between?
- extend through the depths of the retina from the inner surface, where their expanded ‘foot process’ lies adjacent to the inner limiting membrane (ILM)
- to their outer limit, where they have adherens junctions with photoreceptor inner segments to form the external limiting membrane (ELM)
What is the role of Müller cells in the retina and how does this relate to their arrangement?
provide a trellis-basket-like support for the retina, also may help to nourish and maintain the outer retina which lacks a direct blood supply
photoreceptors extend the business end of segments through the gaps in the ELM
What is the arrangement of Müller cells in the retina in relation to other retinal structures?
they envelop blood vessels, neuronal cell bodies and processes, creating glial ‘tunnels’ via a series of cytoplasmic processes
How much glycogen is there in Müller cells?
they contain little glycogen
What 2 organelles are in abundance in the Müller cell cytoplasm and what does this say about their function?
- endoplasmic reticulum
- microtubules
role:
- protein synthesis
- intracellular transport
- secretion
What is the arrangement of Müller cells in relation to astrocytes and what does this allow?
there is extensive coupling, which allows the exchange of tracer molecules
What can be said regarding spatial buffer current between retinal glial cells?
however recent studies have demonstrated an absence of significant spread of spatial buffer curent between retinal glial cells
Both astrocytes and Müller cells have high K+ membrane conductance and most spatial buffer current will flow out through these conductances rather than spreading into neighbouring glial cells through gap junctions
What is chemical coupling like bewteen astrocytes?
sufficiently strong to mediate propagation of intercellular signals such as the spread of metabolites and ions between glial cells.
What is the possible function of chemical coupling between glial cells?
could serve to enhance the transport of key metabolites, such as glutamate, glutamine and lactate, both into and out of glial cells, by allowing them to diffuse between neighbouring cells in the glial syncytium
How do Müller cells increase the efficiency in light capture?
act like fibre optic cables, permitting rapid transmission of photons of light to the photoreceptor outer segments, particularly in fovea/macular area
What are microglia?
highly specialised subpopulation of tissue macrophages that serve as immune sentinels in the parenchyma of the central nervous system
What is thought to be the role of microglia?
role in synapse remodelling (synaptic pruning)
What embryological origin do microglia most likely arise from?
yolk sac erythromeyloid precursors during early development
How may microglia be replenished or self-maintained in adulthood?
by bone-marrow derived circulating monocytes
What morphology characterises microglia?
extremely arborised morphology
What is the immunophenotype of microglia?
resting macrophages
What are the 3 strata in which microglia cell bodies are located?
- nerve fibre layer-ganglion cell layer interface
- one in the inner nuclear layer
- one in the outer plexiform layer
What is formed by the processes of the micoglia?
lateral and vertical three-dimensional network within the retina extending only as far as the outer limiting membrane in the normal eye
What are less arborised subtypes of microglia sometimes referred to as?
perivascular macrophages
What are perivascular macrophages (less arborised subtypes of microglia) homologous with in the brain?
very similar homologous cells in the brain
Where are less arborised subtypes of microglia found (perivascular macrophages)?
perivascular space of retinal capillaries
What are 2 properties that retinal microglia share with brain microglia?
- tissue homeostasis
- host defence
What is the function of the highly arborised processes of microglia?
they are constantly on the move, sampling their immediate microenvironment
What role is played by activated microglia?
role of immune effectors, via the release of chemokines and cytokines
What happens to microglia on injury to the retina?
these cells become activated and assume the role of wandering phagocytes and in disease such as photoreceptor degeneration, retinitis pigmentosa, diabetes, systemic viral infection, or indeed ageing, microglia will migrate into the subretinal space where they may play a role in protecting RPE integrity
What does recent data suggest about heterogeneity of microglia populations?
- those in the inner plexiform layers being IL-34 dependent with a role in synaptic function relating to colour vision
- whereas those in the outer retina are IL-34 independent
What happens to microglia with age?
increasing tendeny to asusme more amoeboid form and activated phenotype and migrate towards the subretinal space
In which region of the retina are age-related changes to microglia most evident?
in the peripheral retina close to age-related cystoid retinal degeneration
What is special about the vascular supply of the retina?
it has the highext oxygen consumption per weight of any human tissue
What are the 2 key functions of the highly selective blood-tissue barrier of the retina?
- regulates the optimal extracellular environment to facilitate neural transmission
- regulates passage of pathogens and intravascular leucocytes, thus partly protecting the neural environment from ‘surveillance’ by immune cells
What type of blood supply does the retina have?
dual blood supply
What is meant by the retina being holangiotic?
having blood vessels present in all parts of the retina
What blood vessels are different parst of the retina supplied by?
- inner two-thirds = central retinal vessels
- outer one-third = choroidal circulation
What is the choroidal blood flow rate?
150mm/s
What are 3 key features of the choroidal circulation?
- high flow rate (150mm/s)
- low oxygen exchange
- fenestrated capillary bed
What are 2 key features of the retinal circulation?
- low flow rate (25mm/s)
- high oxygen exchange
What are 2 key differences between choroidal vs retinal circulation?
- choroidal circulation has high flow rate (100mm/s) while retinal has low flow rate (25mm/s)
- there is a low oxygen exchange in choroidal circulation but high oxygen exchange in retinal
What are the 2 sets of characteristics of the blood-retinal barrier?
- structural character of endothelial and RPE cells at endothelial and RPE tight junctions
- membrane-associated transport characteristics
What is the diameter of the central retinal artery?
0.3mm in diameter
What vessel does the central retinal artery arise from and where?
ophthalmic artery - either in the optic canal or close to the optic foramen where the ophthalmic artery lies bound to the dural covering of the nerve
What is the pathway of the central retinal artery?
- arises from ophthalmic artery (optic canal or close to optic foramen)
- travels forward on undersurface of optic nerve within its dural covering
- 1 - 1.5cm behind the eye, pierces inferomedial aspect of the remainder of meningeal coverings to pass through the subarachnoid and then pierces the nerve
- as it passes forward in the centre of the optic nerve, is accompaneid by the central retinal veins and a few sympathetic fibres
- pierces papilla centrally, having passed through a constriction or gap in the lamina cribrosa
- branches into superior and inferio branches which subdivide into nasal and temporal arteries
What are 2 things which accompany the central retinal artery as it passes forward int he centre of the optic nerve?
- central retinal vein
- a few sympathetic fibres
What is a clinical correlation of the fact that the central retinal artery resembles other muscular arteries?
it is affected by conditions such as atheroma and giant cell arteritis
Where is a potential site for partial or complete occlusive disease of the central retinal artery?
the site where it pierces the central papilla, having passed through a constriction or gap in the lamina cribrosa
What does the central retinal artery branch into once it has pierced the papilla?
- superior and inferior branches
- these subdivide into nasal and temporal arteries
What imaging modality best appreciates and investigates the branches of the central retinal artery?
fluorescein angiography
What may provide a connection between the choroidal and retinal circulations and where?
a small vessel, the cilioretinal artery, which may be pesent near the optic nerve head, providing anastomotic connection between choroidal and retinal circulations
What is the central retinal artery diameter on emerging from the optic disc?
decreases to 100 μm
In what layer do the large retinal arterial branches travel?
in the nerve fibre layer beneath the inner limiting membrane
Which layer of blood vessel wall do the arterial branches of the central retinal artery lack?
internal elastic lamina (lost at the optic disc)
Why are the large retinal branches unaffected in temporal arteritis?
because they have no internal elastic lamina (is lost at the optic disc)
What are the key features of the vessel walls of the large retinal arteries?
- possess a well-developed muscularis
- numerous pericytes lie within the endothelial basal lamina
What is meant when the large retinal artery branches are describes as functional end-arteries?
the branches each supply a sector of the retina between which there is no overlap
Where are the superior and inferior temporal arteries located?
they curve above and below the macula and foveal region
What is the clinical significant of retinal arteries passing over veins?
in some pathological situations they cause ‘nipping’ or narrowing of the veins
How many levels of capillary networks exist in the retina? How are they arranged?
2 main levels - spread like cobweb throughout the retina
What layers are the inner and outer plexuses of capillary networks within the retina situated within?
- inner plexus: level of ganglion cell layer
- outer plexus: inner nuclear layer
Up to how many layers of retinal capillaries may exist in the peripapillary zone?
up to 4 layers
Up to how many layers of retinal capillaries may exist in the perifoveal region and at the ora serrata?
single layers
What is the papilla in the retina?
the optic disc - where it enters eye and joins with the retina
After what timem do irreversible changes occur in complete central retinal artery oclusion?
after 1-2 hours (sometimes quoted as 90-100 minutes)
What happens to the retina in complete central retina artery occlusion?
the inner retina becomes white and oedematous except at the foea, which survives owing to the underlying choroidal circulation, which shows through as a round red patch
What causes the cherry red spot in complete central retinal artery occlusion?
the fovea - due to underlying choroidal circulation
How deeply do retinal capillaries pass into the retinal layers in humans?
only as far as the sclerad margin of the inner nuclear layer
Within which region of the retina are capillaries most dense?
in the macula
Within which region of the retina are capillaries absent and how large is this region?
in the fovea (capillary-free zone 500 μm in diameter)
larger arterioles are surrounded by a capillary-free zone
What is the fovea dependent on for nutritional support and why?
the choriocapillaris - no retinal capillaries in this region
What happens to capillary network density int he retinal towards the peripheral retina?
capillary network density decreases
What is the arrangement of peripapillary capillaries (those around the optic nerve)?
a further lamina of capillaries fans out over the nerve fibre layer in the peripallary region
Why may the unique capillary network of peripapillary capillaries be more vulnerable to raised IOP in glaucoma? 3 reasons
- due to the long course of these vessels (over 1000μm)
- infrequent arterial input
- lack of anastomoses
Within which region in the retina do flame-shaped haemorhages or cotton wool spots predominantly occur?
in the radial peripapillary capillary network
What are flame-shaped haemorrhages caused by?
hypertension or papilloedema
When do cotton wool spots occur?
in ischaemic disease
What is the organisation of the endothelium in retinal capillaries?
complete cicumferentially oriented endothelial cells joined by non-leaky tight junctions (zonulae occludentes)
How does the permeability of retinal capillary endothelial cells compare with that of brain capillaries and how do we know?
the high number of endocytotic vesicles in retinal capillary endothelium suggests they are more permeable than brain capillaries
What structures surround retinal capillaries? 3 things
- thick basal lamina
- pericytes
- astrocyte foot processes
What may be the role of astrocyte foot processes surrounding retinal capillaries?
may act as a second front in the blood-retinal barrier and thus compensate for the more permeable nature of retinal vascular endothelium (are 4x more numerous around retinal vessels than brain capillaries)
What conditions can affect the number of supporting cells around retinal capillaries?
decrease in diabetes, macroglobulinaemia and other ischaemic diseases
What is the luminal diameter of retinal capillaries and how does this compare with conventional capillaries?
3.5–6 μm, somewhat smaller than conventional capillaries (large enough for white cells to squeeze through)
What is the amount of extravascular conentive tissue around retinal vessels like?
there is very little
What cell is absent in the retina but common in other tissues including the choroid?
mast cells
Are there lymphatic vessels in the retina?
no
What is shown in the image?
wide field photograph of the normal human fundus
What is shown in the image?
multispectral digital ophthalmoscopic image of retinal and choroidal circulations
How does multispectral digital ophthalmoscopic imaging capture vesels of the choroidal circulation?
captures high-resolution image data through the retinal and subretinal layers and hence shows the larger vessels of the choroidal circulation. It both expands the examination wavelength range to include image data from invisible wavelengths of light and generates the probe wavelengths to separate specific spectral regions for enhanced visibility and discrimination.
Is intravascular contrast used in multispectral digital ophthalmoscopic imaging for visualising the fundus?
no
Identify the following on the diagram: central retinanl vessels, larger vessels on retinal surface, the retinal capillaries, and the choriocapillaries
