Retina Flashcards
List the 10 layers of the retina
Retinal pigment epithelium
Outer segments (rods + cones)
Inner segments (zonular adherents between photoreceptors and muller cells)
Outer nuclear layer (nuclei of photoreceptors)
Outer plexiform layer (synapses between photoreceptors, bipolar and horizontal cells)
Inner nuclear layer (nuclei of supporting cells)
Inner plexiform layer (synapses of bipolar/amacrine cells occur)
Ganglion cell layer (nuclei of ganglion cells)
Axon fibre layer (axons converging towards optic nerve)
Inner limiting membrane
What is the thickness of the retina?
0.56mm near the optic disc to 0.1mm at the ora serrata
What are the outer and inner surfaces of the retina in contact with?
Outer surface is in contact with Bruch’s membrane of the choroid
Inner surface is in contact with vitreous body
Where does the retina run?
Continuous with optic nerve posteriorly
Extends forward to become epithelium of the ciliary body and iris. Retina extends more anteriorly on medial side, so ora serrata lies closer to the limbus on the medial side
An approximate landmark on the external eyeball is the insertion of MR and LR
What is the embryological origins of the retina?
NEUROECTODERM
Invagination of optic vescile
Day 27
Outer pigment layer derived from outer layer of optic cup
Inner neural layer from the inner layer of optic cup
Posterior 4/5 neuroretina -> rods +cones. 2 layers of the retina are separated by a potential space which is the remains of the optic vesicle cavity
What are the macula lutea and fovea centralis?
Macula lutea is in the posterior part of the retina, yellow oval area which is for the most distinct vision. (5mm) It has a central depression called fovea centralis (1.5mm)
Fovea centralis has only photoreceptors (nerve cells and fibres are displaced peripherally) no blood vessels overlying and no rod cells. Highest concentration of cones to ganglion cells (1:1)
Where is the optic disc in relation to the macula?
3mm to the medial side of the macula
What makes up the retinal pigment epithelium?
Single layer of cells
Narrow and tall in posterior pole, flattened/cuboidal near ora serrata
Highest density in the macula
Tangentially hexagons
Rested on BM which forms part of Bruch’s membrane
Contains melanin
Microvilli
Where is the largest concentration of mitochondria in the body?
On the inner segments of photoreceptors
Mitochondria lie on the outer plexiform layer of the retina but not the outer nuclear layer
Which enzyme can be used as a marker of mitochondria?
Cytochrome oxidase
What is the blood supply to the retina?
- Outer laminae, including the rods and cones and outer nuclear layer are supplied by choroidal capillaries (choriocapillaris). Extends as far as the outer plexiform layer
- Inner laminae are supplied by central artery and vein (end arteries with nil anastomoses)
Neither one of these supplies alone is sufficient
Why is the blood supply to the retina a paradox?
The outer half of the retina is avascular. This is the only part of the CNS to lack vessels, but the photoreceptors have a very high oxygen requirement.
Where are mitochondria found in photoreceptors, muller cells and RPE?
Photoreceptors: elongated mitochondria full the inner segments and press up against the base of the cell’s cilium
Muller cells: mitochondria congregate at the outer end of the cell
RPE cells: mitochondria congregate against the base of the cells
Mitochondria in the retina migrate within their cells towards a source of o2 eg choriocapillaris
Describe the oxygen tension throughout the depth of the retina
2 smaller peaks produced by retinal circulation
Then drops to zero oxygen at inner segments due to massive O2 consumption by photoreceptors
Then a very large peak from choriocapillaris
If inner segments do not consume all the O2, then O2 flows across the retina
Which 2 stress induced proteins cause normal degeneration of the outer cells of the retina?
GFAP (found in Muller cells)
FGF-2 (found in photoreceptors)
Why is the normal retina degenerative at the edge?
Because O2 reaches it from the choroid
Causes cystic/trabecular degeneration
At what age does normal retinal degeneration occur?
Appears as early as 8 years old
Pigment cells migrate in
Why does giving oxygen during retinal detachment limit the thinning of the outer nuclear layer?
Thinning of ONL is caused by death of photoreceptors
This death is caused by hypoxia as the photoreceptors are further away from the choriocapillaris
Detachment also causes proliferation of glial cells in inner nuclear layer->prolferative vitreoretinopathy
Prevented by O2 supplementation
How does the oxygen profile of the retina change in retinitis pigmentosa?
O2 consumption by photoreceptors is eliminated meaning the outer retina now gets heaps of O2
This causes toxicity and thinning of the retinal vessels. Hyperoxia is toxic to photoreceptors
How does the retina change in retinitis pigmentosa?
Becomes pigmented as pigment cells migrate into degenerating retina
Thinning of vessels
Obliterated vessels due to hyperoxia
What are the functions of the pigment epithelial cells of the retina?
Absorption of light
Turnover of photoreceptors
Formation of rhodopsin and iodopsin by storing and releasing vitamin A
Blood retina barrier
What is the blood retina barrier?
Pigment epithelial cells of the retina are joined together by tight junctions which completely encircle the cells
Forms a barrier which limits the flow of ions and diffusion of large toxic molecules from chorioid to photoreceptors of neuroretina.
What are the three main groups of neurons found found in the neural retina?
Photoreceptors
Bipolar cells
Ganglion cells
(also contains amacrine and horizontal cells)
How does the photoreceptors, bipolar cells and ganglion cells work together to conduct impulses?
Photoreceptors- similar to other sensory receptors
Bipolar cells are similar to cells in posterior root ganglia and form first order neurons
Ganglion cells are similar to relay neurons found in spinal cord and form second order neurons. Axons become myelinated after passing through lamina cribosa (myelin formed by oligodedrocytes)
Nerves of lateral geniculate body form 3rd order neurons and their axons terminate in visual cortex
What are the two types of photoreceptor?
Rods and cones
What are the key differences between rods and cones?
Rods: dim light, produce black and white images
110-123 million. Absent from fovea +increase in number around periphery. Then diminish in number at extreme periphery.
Cones: colour, clear vision. 6.3-6.8 million. Most dense at fovea and sparse around periphery.
Describe the rod cells
Slender cells (100-120 microns long) Outer segment= true photoreceptor. Contains membrane bound discs like a pile of coins. Contain rhodopsin. When the top of the coin pile reaches pigment epithelium it is phagocytosed. Most discs are shed in early morning.
Connecting stalk: modified cilium
Inner segment: ellipsoid (mitochondria) and myoid (ER, golgi apparatus, ribosomes).
Describe the cone cells
Slender cells (65-75 microns) Outer segment= conical in shape. Discs are continuous with outer plasma membrane Tips not phagocytosed by pigment cells. Contains iodopsins
Connecting stalk: modified cilium
Inner segment: same as rod
What are the different types of bipolar cells?
Rod: connect several rod cells to one to four ganglion cells
Flat: connect many cone cells with many ganglion cells
Midget: single cone cell with single ganglion cell
Where are the most ganglion cells found in the retina?
Most of the retina form a single layer
Number increases from periphery to macular, where there may be 10 layers
Absent from fovea
What is the lamina cribosa?
Weakest part of the sclera
After piercing lamina, ganglion cells become myelinated
What are horizontal cells?
Multipolar cells near to rods and cones
Respond to neurotransmitter liberated by the rods and cones following excitation by light
Then liberate GABA which inhibits bipolar cells some distance away, sharpening contrast
What are amacrine cells?
Large cells bodies situated close to ganglion cells
Stimulated by bipolar cells and excite ganglion cells
25 different types
What are muller cells?
Long pale staining cells
Fills up most space in neural retina not occupied by neurons
Surround and support nerve cells
Layer of zonulae adherents forms a dense staining line called outer limiting membrane
Transport neuromodulators
Nourish outer retina
What are the 5 layers of the Bruch’s membrane?
RPE basal lamina Inner collagenous zone Middle elastic layer Outer collagenous zone BM of RPE Endothelium of choriocapillaris
Where is the retina firmly attached?
Optic disc margin
Anteriorly at ora serrata
What is the function of melanin in RPE cells?
Free radicals
Loss of melanin associated with albinism and age related macular degeneration
What is the function of the glycosaminoglycans which surround the microvilli of the retinal pigment epithelial cells?
Act as a glue to bind the pigment layer to neural layer
What binds adjacent retinal pigment epithelium cells together?
Zonula adherens- basal region
Zonula adherens- apical
Form tight junctions which isolate the retina from the systemic circulation
Describe bipolar cells
Most nuemrous of supporting cells
35 million in retina
Parallel to photoreceptors
Connect photoreceptors to ganglion cells and amacrine cells
Synapse with photoreceptors in outer plexiform layer
Synapse with amacrine cells and ganglion cells in the inner plexiform layer
How does the ratio of photoreceptors to bipolar cells change throughout the retina?
50-100 rod cells to 1 bipolar cell
1:1 in fovea
Which type of cone cell is the most numerous?
Long/ red cone
Short/blue cones make up less than 10% of the retina cones
Where do RPE cells get their blood supply?
Choriocapillaris
What are the functions of the RPE?
Absorption of light via melanin Blood retinal barrier Secretes VEGF +GAGs Transports nutrients ions and water Phagocytosis of outer segment photoreceptor discs Vitamin A storage and metabolism
In which layer does retinal detachment usually occur?
Between RPE and photoreceptors
Where does the optic nerve run?
Optic nerve is surrounded by meninges (unlike other peripheral nerve)
Extends from globe (above and 3mm medial to posterior pole) at optic nerve head to the optic chiasm in cranial cavity
What are the 4 parts of the optic nerve and how long are they?
Total length 5cm Intraocular optic nerve head (0.07cm) Intraorbital (3cm) Intracanalicular (0.6cm) Intracranial (1cm)
Where does the optic nerve sit and what occurs there?
Extends from retinal surface, in contact with vitreous to myelinated portion of the optic nerve
Ganglion cell axons converge here and exit globe through lamina cribosa
Site of entry/exit of retinal vessels
What are the dimensions of the optic nerve head?
Mean disc area: 2.69mm Horizontal disc width: 1.76mm Vertical disc width: 1.92mm Cup/disc ration: 0.43 Diameter expands from 1.8mm to about 3mm behind sclera where neurons acquire myelin
What are the divisions of the optic nerve head?
Surface nerve fibre layer
Prelaminar region
Lamina cribosa region
Retrolaminar region
What is the histology of the superficial nerve fibre layer of the optic nerve?
Innermost layer
Covered by inner limiting membrane of Elschnig (astrocytes) which is continuous with Muller cells
Glial cells and interaxonal processes are sparse
Astrocytes-10% of OPH volume, the rest are axons
What is the histology of the prelaminar region of the optic nerve head?
Anterior portion of lamina cribosa
Trabeculae between axon bundles carry capillaries which are surrounded perivascular connective tissue and limiting membrane from glial footplates
Degeneration of hyaloid artery leaves surrounding neuroglial cells to persists as central tissue meniscus of Kuhnt
Only astrocytes-no oligodendrocytes
What is the border tissue of Elschnig?
Rim of sclera at the scleral foramen
Dense collagenous tissue with elastic and glial fiber
What is the border tissue of Jacoby?
Separates optic nerve fibres from retinal layers.
Cuff of astrocytes separating axons from choroid and scleral canal
Intermediary tissue of Kuhnt is a forward extension of the border tissue of Jacoby
Continues posteriorly as glial mantle
Describe the histology of the laminar region?
3-10 dense connective tissue sheets across scleral foramen which blend with sclera peripherally
More prominent posteriorly
Transmits axon bundles of optic nerve and central retinal artery
Each trabeculae has collagen, elastic fibres and vessels (due to in growth of circle of Zinn during development)
Glial cells line trabecular beams
Describe the histology of the retrolaminar region?
Myelinated nerve axons
Accounts for the doubling of the optic nerve diameter after traversing the lamina cribosa
Invested into the sheath of dura, arachnoid and pia mater
Contains supporting astrocytes, oligodendrrocytes and microglial cells
Why does the ONH have late floursecence with fluouroescein angiography?
No tight junctions
What is the difference between choroidal crescent and scleral crescent?
Choroidal: where retinal falls short of the optic nerve
Scleral: where retina and choroid fall short of the optic nerve
How does the choroid meet the optic nerve?
Basal lamina of Bruch’s membrane ends at the entry of the ON
Vascular choroidal stroma ends further from the disc
Stromal lamellae is separated from ON by border tissue
How does the sclera meet the optic nerve?
Scleral fibres become circular towards the surface and interlace with the longitudinal fibres of the dura
Marginal tissue of Elschnig separates sclera and choroid from optic nerve
What is the blood supply to the retrolaminal ONH?
Pial sheath recurrent branches 2’ + 4 and longitudinal arterioles 3 + 3’
Scleral short posterior ciliary artery
Circle of Zinn-Haller
Central retinal artery
What is the blood supply to the laminar ONH?
Circle of Zinn-Haller (intrascleral anastomosis)
Formed by branches of the short posterior
ciliary artery
Circle may be complete or incomplete
What are the branches of Circle of Zinn-Haller?
Recurrent pial branches Recurrent chorioidal branches Direct branches Arteriolo-arteriolar anastomoses Interfacial precapillaries Anastomoses larger posteriorly
What is the blood supply to the prelaminar ONH?
Scleral short posterior ciliary artery and recurrent choroidal arteries
What is the blood supply to the surface ONH?
Pericapillary and epipapillary arterioles of central retinal artery
Lots of anastomoses including occasional anastomoses with choriocapillaris
What is allowed to pass through the blood brain barrier at the optic nerve head?
BBB is incomplete
Plasma diffusion occurs
Protein entry to retina is blocked by tight junctions and RPE cells
What is the venous drainage of optic nerve head?
Central retinal vein
Small number drain into pial veins
Small number into choroidal system
Describe the embryology of the ONH
24 days: optic stalk
7 weeks: ganglion cells extend towards optic stalk
8 weeks: lamina cribosa begins, optic tract develops
11wks: connective tissue and vessels penetrate
16-17wks: optic nerve axon count peaks at 3.7 million, declines to 1.2 million at term
What shape is the optic cup usually?
Oval
Vertical diameter 9% longer
8% wider horizontally
Describe the retinotopic organisation of nerve fibres
Ganglion axon cell course very precise towards optic nerve, less precisce towards the chiasm
Axons from fovea are central in the ON
Temporal nerve fibres remain on the same side and nasal ones cross at the chiasm
What are the common patterns of optic disc visual loss and their causes?
Central scotoma: optic neuritis, tobacco alcohol ambylopia, compression
Altitudinal: ischaemic optic nueropathy
Enlargement of blind spot: early papilloedema
Nasalfield: secondary optic atrophy
Arcuate: disc drusen
What does a retinal capillary look like under the microscope?
Cell nuclei
Tight junction
Vascular basement membrane
Pericyte
How is retinal autoregulation achieved?
Changes in resistance of retinal vascular tree
Wha causes changes retinal vascular tone?
Nitric oxide- vasodilator
Endothelins-vasoconstrictor
Retinal renin angiotension system ang2 constricts, bradykinin- dilates
Acts on pericytes and smooth muscle
What the blood retinal barrier do?
Controls flux of fluid and blood borne elements into neural parenchyma
Loss of BRB causes loss of vision
Maintains metobolites between glia and neurons
Tight control of ionic environment
Provision of excitatory amino acids eg, glutamate
What are the layers of the BRB?
Inner BRB- retinal blood vessels
Outer BRB- RPE
Tight junctions (claudins, occludin) and adherens junctions (cadherin, beta catenin)
Claudin 5 is in vascular endothelium. Linked to actin cytoskeleton by adaptor proteins (ZO)
Describe the transport across the BRB
Para and transcellular
Passive: lipophilic substances
Active: Glut-1, fluroscein
Receptor mediated endocytosis: Transferrin, IGF and Insulin
How do the glia (Muller cells) contribute to BRB?
Close contact of astrocytes and muller cells to retinal vessels
Co-culture of muller cells +endothelial cells increases barrier function
Disruption of Muller cells induces telangiectasis and leak
What causes BRB breaksown?
Increased VEGF
Inflammation
Oxygen free radicals
Which diseases cause BRB breakdown?
Diabetic retinopathy RVO Uveitis RP AMD Radiation
What are the two most common retinal vasculopathies?
- Diabetic
2. Retinal vein occlusion
What are the contributing factors to diabetic retinopathy vascular disease?
High glucose-> glycosylation end products, polyol pathway, activation of Protein Kinase C, reactive O2 species Leukocyte infilitration Pericyte death VEGF production Neural apoptosis Genetic susceptibility
What are the different varieties of macula oedema?
Focal diabetic macula oedema
Diffuse macula oedema
Ischaemic macula oedema
What are the issues with laser therapy in DME?
- Laser does not improve vision
- Many people lose vision despite laser
Some DME does not respond well to laser
What are the modern treatments for diabetic retinopathy?
Intra vitreal steroids and anti- VEGF
What are the side effects of steriod use?
Cataracts
Glaucoma
Infection
What did the clinical trials of laser vs ranibizumab suggest?
Ranibuzumab and ranibuzumab +laser treatment is vastly superior to laser in terms of visual acuity and mean CMT change
