20.3 Vision Flashcards
What is the retina?
The retina is a layer structure composed of an epithelium and neurons that transduce light into an electrical stimulus and process it, before transmitting it via the optic nerve
Perceptive opening for retinal processing
-
The eye is a clinician’s window into the brain
- not least of all because the retina is an extension of the CNS but the arrangement of blood vessels and the optic nerve sheath can provide information on the intraoccular and intracranial pressures as indicators of disease.
- Similarly, the pupillary light reflex can be used to assess the function of the brainstem and optic nerves.
- This is because the retina has the sole responsibility of transducing the light into an electrical impulse which is then conducted via the optic nerves to higher brain centres.
- However, retinal function is not limited to transduction.
- The retina is comprised of complex circuits that process information from the 127 million photoreceptors and compress it into just 1 million optic nerve fibers.
What are the three main histological parts of the anterior eye?
- Cornea
- Scelera
- Conjunctiva
Outline the layers of the cornea
EBSDE
-
Epithelium
- 5-7 cells thick
- High turnover
- Prevents bacterial entry
-
Bowman’s membrane
- Dense, thin connective sheet
- Forms the junction between the epithelium and the stroma
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Stroma
- Regularly arranged, parallel type 1 collagen fibres are organised into fibrils
- Fibrils form lamellae which are equally spaced, making the cornea clear
- Mucopolysaccharides to embed the fibrils
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Descemet’s membrane
- Separates the stroma from the underlying endothelium
-
Endothelium
- Singe layer of cells
- Deepest surface is covered in aqueous humour
Outline the function of the scelera
- Attachment for extraocular muscles
- Anterior 1/3 = joins choroidal tissue to form the lamina cribrosa
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Posterior 2/3s = continous with the dura mater
- Scelera - ESLEL
- Endothelium
- Stroma
- Lamina fusca
- Episcelera
- Lamina cribosa
- Scelera - ESLEL
Outline the histological layers of the scelera
ESLEL
-
Episclera
- Loose fibrous elastic tissue
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Stroma
- Irregular type 1 collagen fibres
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Lamina fusca
- High count of pigmented cells
- Dense capillary plexus
- Endothelium
-
Lamina cribrosa
- Fenestrated region of the scelera which the optic nerve exits from
- Collagen lattice that maybe compressed
- Supports the toptic nerve as it exits the eyeball
- Forms a boundary to oligodendrocytes
- Myelination would decrease the transparency of the retina
What does the conjunctiva cover? What is its structure?
- Covers the anterior eye scelera, inner eyelids but not the cornea
- Structure
- Non-keratinised, stratified squamous
-
Interspaced goblet cells
- Secrete gel forming mucins
- Contains:
- Blood vessels
- Lymphoid tissue
- Fibrous tissue
What value of intraoccular pressure would be indicative of raised intraoccular pressure and what are the potential consequences?
- Normal IOP = 16.5 mmHg
- Raised IOP e.g. in glaucoma results in compression of the collagen lattice
- At around 21 mmHg, the optic nerve head is compressed
- Results in conduction block and can cause permanent damage and blindness
What are the two main layers of the retina?
-
Inner sensory retina
- Layers of nerve cells that span from the deep pigmented epithelium to the vitreous humour anteriorly
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Outer retinal epithelium
- Simple cuboidal epithelial cells with melanin granules
- Dark pigments
- prevent the reflection of light within the posterior chamber of the eye
Histology of the inner sensory retina
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Deep (pigmented epithelium)
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Layer of photoreceptor outer segments
- The outer segment of the photoreceptor contains the light sensitive elements
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Outer nuclear layer
- The outer nuclear layer contains the cell bodies of the photoreceptors
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Outer plexiform layer
- The outer plexiform layer contains the synaptic connections between the photoreceptors, bipolar cells and horizontal cells
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Inner nuclear layer
- The inner nuclear layer contains the cell bodies of bipolar cells, horizontal cells and amacrine cells
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Inner plexiform layer
- The inner plexiform layer contains the synaptic connections between the bipolar cells, ganglion cells and amacrine cells
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Ganglion cell layer
- The ganglion cell layer contains the cell bodies of the ganglion cells
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Layer of photoreceptor outer segments
- Superficial (vitreous humour)
- Describe the segments of photoreceptors
- Inner segment
- Mitochondria
- Golgi body
- RER & SER
- Outer segment
- Stacks of membranous discs with photo pigment
- Describe the rods and cones in terms of:
- Outer segment shape
- Termination shape
- What they synapse onto
- Their photo pigment
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Rods
- Outer segment shape -cylindrical
- Termination structure - rod spherule
- Small knob
- Synapse onto - bipolar and horizontal cells
- Photo pigment - rhodopsin
- Night vision
- Low resolution
-
Cone
- Outer segment shape - conical
- Termination structure - cone pedicle
- Thicker
- Synapse onto - bipolar and horizontal cells
- Photo pigment - photopsin
- High resolution detail
- Discriminates primary colours
Outline the types of cones and their wavelengths
- S
- 445 nm
- Blue
- M
- 535 nm
- Green
- L
- 575 nm
- Red
What are the different types of retinal cells? What are their functions?
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Muller glial cells
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Present in all layers
- Nuclei in the inner nuclear layer
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Cytoplasm spans the length of the lamina
- Cytoplasmic processes fill the gaps betwen other retinal cells
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Regulate neuronal exictability
- Monitoring:
- Extracellular K+
- Uptake of neurotransmittter at synapses
- Monitoring:
-
Present in all layers
-
Horizontal cell
- Branch to the photoreceptors and bipolar cells in the outer plexiform layer
- Present in the outer edge of the inner nuclear layer
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Bipolar cells
- Rod specific cells
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Cone specific cells
- Cone bipolar cell have 2 subtypes
-
Midget
- Single cone photoreceptor to a single ganglion cell
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Parasol
- Connect several cone photoreceptors to a single ganglion cell (convergence)
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Midget
- Each subtype can have ON/OFF cells
- Cone bipolar cell have 2 subtypes
-
Ganglion cell
- 3 main types that feed into the lateral geniculate pathways:
- Midget = parvocellular
- Parasol = magnocellular
- Bistratified = koniocelular
- Each have ON/OFF that can be found in separate sublamina
- On = sublamina A of the inner plexus layer
- Off = sublamina B of the inner plexus layer
- 3 main types that feed into the lateral geniculate pathways:
- Outline the difference between midget cells and parasol cells in terms of:
- Soma size
- Dendritic field size
- Concentration
- Colour
- Summation
- Longetivity
- Projections
- Receptive field size
- Conduction velocity
- Pathway to the lateral geniculate nucleus
What is the fovea?
- Area of highest visual colour acuity and is at the centre of the gaze
- There is a 1:1 relationship between photoreceptors and ganglion cells
- Area containing the highest density of cone photoreceptors
- Present within the macula of the retina
- The other cell layers are pushed aside to reduce the blur from light scattering by other cells
What is the optic disc?
- Where axons of the ganglion cells converge and emerge from the back of the eye
- AKA blind spots
- No photoreceptors are present and is nasal to the fovea
- Light never falls on the blindspots of both eyes simultaneously
Describe the photoreceptor distirbution across the retina
-
Fovea
- Contains predominanty red/green cone (LMS)
- 575 nm = red
- 545 nm = green
- 445 nm = blue
- Few
- No rods present
- Contains predominanty red/green cone (LMS)
- Peripheral retina
- Some cones are present - but not in high densities like the fovea
- More rods in these areas
What is the role of pigmented eptihelium?
- Choroid = vascular layer between the retina and scelera
- Prevent reflection of light posteriorly
-
Transport nutrients
- from the choroidal blood vessels to the sensory retina layers
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Removal of waste metabolic products
- from the sensory layer
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Active phagocytosis and recycling
- of photoreceptor disks shed from cones and rods
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Synthesis of basal lamina of Bruch’s membrane
- Bruch’s membrane = inner most layer of choroid layer that attach the pigmented retina
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Formation of rhodopsin
- converting the bleached pigment into retinal and returning it to the rods via intersitial retinoid binding protein (IRBP)
What is retinal detachment?
- Separation of the fovea from the optic disc
- Caused by:
- Trauma
- Vascular disease
- Metabolic disorders
- Risk factors
- Myopia
- If detached for long enough, the sensory retina can become necrotic and this can lead to blindness
- Treatment
-
Retinal layers can be surgically reattached
- Cryotherapy
-
Retinal layers can be surgically reattached
Outline the equation for optical refractive power of the eye (P) and the contributions of different eye components
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P = µ/f
-
µ = refractive index of media of the eye
- 1.33 (approximately that of water)
- f = focal length of the eye
- 0.022 m
- P = 60 dioptres
-
µ = refractive index of media of the eye
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Cornea
- 42 dioptres
- Non adjustable
- 42 dioptres
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Lens
-
18 doptres
-
Adjustable - accommodation via ciliary muscles
- Contraction of annnular ciliary muscles which reduces tension in radial zonular fibres, allowing lens to relax to a more convex state
- Contract to thicken lens
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Parasympathetic of M3 muscarinic receptors
- Gq
- Allows focus on close by objects
-
Adjustable - accommodation via ciliary muscles
-
18 doptres
- Air/cornea interface (42 dioptres) causes more refraction than lens/aqueous humour interface (18 dioptres)
Define 1 dioptre
The power of a lens to focus parallel light at a focal point 1 m away
How does the eye accommodate to near vision?
- Increase in power
- Ciliary muscles contract
- Pulling border of choroid towards lens
- Reduces tension in radial zonular fibres
- Suspensory ligaments relax
- Lens becomes thicker and rounder
How does the eye accommodate to distance vision?
- Decrease in power
- Ciliary muscles relax and border of choroid moves away from lens
- Suspensory ligaments pull against lens
- Lens become flatter, focusing on distant objects
Describe myopia and its correction
- Light is focused in front of the retina
- The eyeball is too long (not due to the curvature of the cornea)
- Corrected by negative power concave lenses
Describe hypermetropia and its correction
- Light is focused behind the retina
- Corrected by postive power - convex lenses
- The lens is convex so can accommodate for it by contraction of the circular ciliary muscles that increase refraction
- Accommodation means it may not manifest until later in life
Describe astigmatism and its correction
- Astigmatism = curvature of the cornea in different axis
- Results in different focuses in different lanes of light
- Horizontal point of focus = further back
- Vertical point of focus = in front
- Corrected with spectacles that have a cylindrical component on their surface curvature
Describe presbyopia
- Failure of lens accommodation with age as the lens becomes stiffer and less elastic
- Near sighted vision becomes more difficult
What are cataracts and how can they be treated
- Lens become cloudy
- Higher incidence with dehydration
- Perhaps due to change in salt conditions
- Surgically removed and replaced with an artificial lens
Describe phototopic conditions and the effect on rods and cones
- Vision in the day
- Rods
- Bleached and saturated at -65mV
- Cones
- Active
Describe mesopic conditions and their effect on rods and cones
- Between night and day (indoors - low)
- Rods
- Active
- Cones
- Active
Describe scotopic coniditions and their effect on rods and cones
- Vision in the dark
- Rods
- Active
- Cones
- Not bleached as easily
Define phototransduction
- The process by which light hitting the retina is converted into an electrical, graded potential by photoreceptors
- Results in photoreceptor hyperpolarisation in light
- Due to an intracellular biochemical signalling cascade
- Results in photoreceptor hyperpolarisation in light
Outline the basic stages of the phototransduction cascade
POT PHS
- Photopigment
- Opsin
- Transducin
- PDE
- Hyperpolarisation
- Synaptic transmission
Outline in detail step 1) photopigment in the phototransduction cascade.
POT PHS
- Light energy (electromagnetic radiation or photon particle) is absorbed by photopigments embedded in the membrane of the photoreceptor outer segment discs
- In rods, the pigment is rhodopsin, a complex of the GPCR opsin and the covalently-linked (prebound) agonist retinal
- In cones, the pigment is photopsin a complex made of one of three opsins (L, M, S) and retinal
- RGB = LMS
- Each type of cone produces a different variant of the opsin protein that distinguishes their absorption wavelength
- Red light excites L the most
- Green light excites M the most
- Blue light excites S cones the most
Outline in detail step 2) opsin bleaching of the phototransduction pathway
POT PHS
- Each photpigment contains retinal and opsin
-
Retinal is a small molecule in which the C11-C12 double bond assumes the cis configuration in the dark
- Absorption of one photon by retinal converts the bond to the trans configuration, changing its molecular conformation
- Activates the opsin to metarhodopsin II
- Process is known as bleaching of the photopigment because the pigment changes colour from purple to yellow
Outline step 3) transducin of the phototransduction pathway
POT PHS
- The activated opsin (metarhodopsin II) stimulates the G-protein transducin which then stimulates photphosdiesterase
- Transducin activated through the exchange of GDP for GTP
- The alpha-GTP subunit diffuses laterally through the disc membrane and activates the membrane bound phosphodiesterase (PDE)
- The G protein activity is increased by GAPs (G-protein activating proteins)
- The more metarhdosopin II, the greater the amplification
Describe step 4) PDE of the phototransduction pathway
POT PHS
- PDE degrades cytosolic cGMP to 5’-GMP leading to a fall in [cGMP]i
Describe step 5) hyperpolarisation of the phototransduction pathway
POT PHS
- The reduction in [cGMP]i causes closure of non-selective cation channels in the photoreceptor plasma membrane, reducing the inward Na+ current (the dark current) and hyperpolarising the membrane
- Going from -35 mV to -65 mV
- This slows the release of neurotransmitter from the photo receptor
- In the dark, [cGMP]i is high thus channels are open and transmit a larger inward Na+ current (the dark current)
- The resting Em of the photoreceptor is therefore -35mV and stimulation by light drives the Em in the negative direction to a peak of around -65 mV
Describe step 6) synaptic transmission of the phototransduction pathway
- Hyperpolarisation of the photoreceptor membrane (from reduces Na+ influx) reduces Ca2+ influx through the non-specific cation channel thereby decreasing the rate of glutamate secretion from the synaptic terminal
- In the dark, glutamate is constituvely released becuase the Em is held at a depolarized value (-35 mV)
What are the three main mechanisms in which the photoreceptor signalling cascade is terminated? What is the importance of these mechanisms?
- Mechanisms (RIT)
- Reduction in calcium increases affinity of cGMP channel for cGMP
- Inactivation of metarhodopsin 2
- Transducin GTPase activity
- Importance
- Allows the photoreceptor to be sensititive to another photon of light
Describe how the inactivation of metarhodopsin II results in the termination of the photoreceptor signalling cascade
- Metarhodopsin II is inactivated by rhodopsin kinase which phosphorylates it
- This is followed by the binding of arrestin 2- blocking the interaction its interaction transducin (preventing PDE activation)
How does transducin GTPase acitivty terminate the photoreceptor signalling cascade?
- Active transducin has intrinsic GTPase activity
- Converts the bound GTP to GDP
- Releases the GDP and recombines with its beta-gamma subunits
- cGMP concentration is then restored by guanylate cyclase that converts GTP to cGMP
- The [cGMP] rises, the cGMP channels open and the Na+ current is resumed, membrane back to depolarised dark potential, glutamate is released again
How does calcium concentration result in the termination of the photoreceptor signalling cascade?
- Reduction in the [Ca2+] in the light results in:
- Start - Accelerated rhodopsin kinase phosphorylation of metarhodopsin II
- Middle - Accelerated guanylate cyclase activity (producing cGMP from GTP)
- End - Increased affinity of the cGMP channel for cGMP
- Calcium channels enter the cell via the cGMP channel but are quickly pumped back out by membrane transporters
- Thus during the dark, the [Ca2+] in the cell are higher than in thelight when cGMP channels close
Describe how the rods and cones adapt to a darkly lit environment
- In the light, rod photo pigment is bleached
- -65mV
- Trans-retinal
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Dark Adaptation
- When moving to the dark, the photopigment is able to regenerate and the rods become more sensitive to light
- Metarhodopsin kinase regenerates metarhodopsin
- Trans-retinal back into cis-retinal
- This means overtime, more rods are available to detect the light and transduce it
- Dark adaptation takes around 1 hour to reach maximal sensitivity
- When moving to the dark, the photopigment is able to regenerate and the rods become more sensitive to light
-
Light Adaptation
- The huge increase in light sensitivity in dark adaptation means there is a temporary saturation of photoreceptors upon re-entry into light
- All the rhodopsin is bleached and ganglion cells discharge action potentials, leading to everything appearing white
- After this, light adaptation occurs and the cones become adapted to the light level
- The huge increase in light sensitivity in dark adaptation means there is a temporary saturation of photoreceptors upon re-entry into light
Describe how the eyes adapt to well-lit environments
- In the dark, the cones are inactive
- In the light, the cones become activated and adapted to the level of light
- The use of rods and S cones is shifted to R/G cones in photopic light = Purkinje shift
- tendency for the peak luminance sensitivity of the eye to shift toward the blue end of the color spectrum at low illumination levels as part of dark adaptation)