Retinal Dystrophy Flashcards
where does the retina lie
back of the eye
it is part of the CNS - an outpost of the brain
has several layers of cells
how does light hit the retina
light passes through cornea, enters pupil to lens and then finally falls on retina
what is the vertebrate retina
complex layered structure performing all initial steps of visual processing
7 cell types (expressing different wavelengths)
three nuclear layers (where you find cell body)
two synaptic layers (between nuclear layers)
outline retinal organisation
outer nuclear layer (ONL)
inner nuclear layer (INL)
ganglion cell layer (GCL)
glial cells : Muller cells
synaptic layers: outer plexiform layer, inner plexiform layer
what does the outer nuclear layer contain
photoreceptors: rods and cones
what does the inner nuclear layer contain
horizontal cells
bipolar cells
amacrine cells
cell bodies of all retinal interneurones
what does the ganglion cell layer contain
ganglion cells (output cells, axons form the optic nerve)
displaced amacrine cells
output layer
axons bundle together and form the optic nerve in optic disc - transmitt all info of our visual world on the brain
what does the outer plexiform layer contain
synaptic contacts between photoreceptors, horizontal and bipolar cells
what does the inner plexiform layer contain
synaptic connections between bipolar, amacrine and ganglion cells
divided into ON and OFF layer
what are glial Muller cells
large cells spanning entire thickness of retina
provide srtructural and metabolic support to other cells
what is attached tot he back of the eye
black epithelium, retinal pigment epithelium which interdigitates with outer part of photoreceptors
what is retinal pigment epithelium
feeds receptors, absorbs scattered light
what is choroid
network of blood vessels
what divides the RPE from the choroid
Bruch’s membrane
what is the function of the inner limiting membrane
separates retinal ganglion cells from vitreous humour
very tough membrane made from many proteins
which layer does light enter the retina through
the retinal ganglion cell layer and passes through all the layers to reach the photoreceptors in the outer nuclear layer
what is the fovea
macula,
dark central area devoid of blood vessels
2 degrees of visual angle
temporal part of retina
what is the optic disc
6 degree of visual angle
located 15 degrees nasal to fovea
RGC axons converge and leave eye together with blood vessels
no receptors here
corresponds to the blind spot
BLIND SPOT BECAUSE THERE ARE NO PHOTORECEPTORS ABOVE THE DISC - cant generate images but conscious about it as brain fills it in from perception
outline the fovea
part of the retina, it is a depression in the retina (foveal pit), it is thinner because light comes from above it and can fall directly on photoreceptors and doesnt have to go through all neurons - only rods and cones
no blood vessels, no RGC, no INL, contains only CONES
do rods and cones have the same distribution across the retina?
no
cones are maximally concentrated in the fovea and not anywhere else
rods are everywhere expect fovea
optic disc - no rods or cones
what is the retinal code
retinal ganglion cells are the only spiking neurons, and so convey visual information in the form of spike trains
what neurotransmitter forms vertical connections in the retina
glutamate - photoreceptors, bipolar cells, ganglion cells
what neurotransmitter forms horizontal connections in the retina
GABA (horizontal and amacrine cells)
glycine (amacrine)
acetylcholine (amacrine)
dopamine (amacrine)
horizontal connections are mostly inhibitory
what are the only cells which generate action potential
ganglion cells - retinal code
all other cells have slow graded potential
what is the function of the retina
converts light into electrical signal (phototransduction)
processing in retinal neuronal networks - conveys info on luminance, contrast, colour and also on more complex image features e.g orientation, motion
where do spike trains travel
a.p generated in RGC travels down optic nerve to brain where they are further processed and interpreted to generate visual perception - RETINAL CODE
outline peripheral vision
rods, distributed throughout retina
responsible for ability to see in dim light (scotopic vision)
high sensitivity (detect 1 photon)
only operative at low light levels
scotopic vision is MONOCHROMATIC
low resolution images (poor spatial acuity)
slow temporal responses to change in illumination
outline central vision
cones - concentrated around the fovea
work only in daylight (photopic vision)
low sensitivity - but operates at very broad spectrum of light intensity
photopic vision is CHROMATIC (colour vision)
high spatial acuity
narrow angle of coverage - as fovea is small
fast response to changes in illumination
what would vision look like if the peripheral retina was affected
black on periphery with hole to see through
what would be seen if central retina was affected
monochromatic vision with centre being blurry
what does spectral sensitivity mean
probability of capturing a photon of light at each wavelength
outline the spectral sensitivity of rods
absorb only one wavelength - peak absorbance at 498 nanometres
outline the spectral sensitivity of cones
trichromacy theory
short wavelength - 420nm, blue
medium wavelength - 534nm, green
long wavelength - 564nm, red
balance of the three determines our perception of colour
what is phototransduction enabled by
visual pigment in outer segment disc
the pigment is an opsin + chromophore - derived from vitamin A (manufactured from beta-carotene in food)
retina is attached to chromophore formation when hit with light - if not bound then no response
outline how phototransduction works
light (photons) activate opsin which changes conformation
-> closes cGMP-gated Na+ channels in outer segment membrane
calcium also fluxes in and out
stronger light flash = stronger membrane hyperpolarisation
= channels close in light
after the membrane is hyperpolarized in photoreceptors what happens next
causes either depolarization or hyperpolarization in bipolar cells - leads to response in RGC (output channel of the retina)
why are horizontal cells in outer retina important
delimit receptive field centre-surround (contrast sensitvity)
why are amacrine cells in the inner retina important
temporal aspects of light responses (transient vs. sustained responses)
how many cones are there
6 million
what is spatial acuity of the cone pathway enhanced by
- dense packing of the cone array
- 1 to 1 convergence of cones onto RGCs at the foveola
how many rods are there and where are they all packed
120 million
densely packed in periphery but many rods contact one RGC
what are the types of optic neuropathy
diabetic retinopathy - microvascular retinal changes
mitochondrial disorders - Leber’s hereditary optic nerve neuropathy
multiple sclerosis - optic nerve demyelination (conduction problems)
glaucoma - high intraocular pressure RGC death (optic disc is swollen)
outline optic neuropathy
RGC and optic nerve degeneration
light can still be converted to neural signals (as photoreceptors not dead) but communication with visual centres of brain is lost
outline photoreceptor dystrophy
photoreceptors degenerate
light cannot be converted into neural signals but retina can still communicate with visual centres of the brain - because ganglion cells in the optic nerve are intact
rods first then cones
e.g Retinitis Pigmentosa
hereditary disorder rod degeneration
what are the symptoms of photoreceptor dystrophy
night blindness (nyctalopia)
followed by tunnel vision (reduction in peripheral visual field)
may be followed by loss of central vision at late stages
what is a main type of photoreceptor dystrophy
age related macular degeneration (AMD)
outline amd
affects elderly
cone (macula) degeneration
starts with yellow lipid deposits called DRUSEN in macula, between RPE and underlying choroid
outline dry AMD
DRUSEN become larger and more numerous, accumulate between retina and choroid, cause damage to RPE underlying macula
retina can become detached
outline wet AMD
more severe
blood vessels grow from choroid into retina through Bruch’s membrane
retina becomes detached
is it possible to restore visual perception in optic neuropathies
not at retinal level because RGCs and optic nerve have degenerated
-> visual centres of brain have to be stimulated directly - challenging
is it possible to restore visual perception in retinal dystrophy
yes, it is possible to restore at retinal level
how can visual loss in retinal dystrophies be reversed
by direct stimulation of retinal ganglion cells, bypassing the degenerated photoreceptors
what is the method of how visual loss is reversed in visual dystrophies
create light perception (phosphene) in blind person by stimulating small area of RGC
array of stimulating electrodes (epiretinal/subretinal) powered by cables or transcutaneous telemetry systems
emulate retinal code artifically
what are some other therapeutic approaches
stimulation of the optic nerve with a cuff electrode
but this is imprecise
- or direct stimulation of visual cortex
outline subretinal implants
inserted into subretinal space, stimulating electrodes placed between degenerated photoreceptors and surviving INL and RGC layers
what is an advantage of subretinal implants
configuration is taking advantage of remaining synaptic connections converging into RGCs (although these connections are not normal)
easy to maintain implant in place
what are technical challenges of subretinal implants
major surgery for implantation
not easily accessible to remove for replacement with upgrade model
stimulation thresholds are high
what are epiretinal implants
in direct contact with ganglion cell layer
what is an advantage of epiretinal implants
easily accessible to remove for replacement with upgrade model
stimulation threshold is lower
what is a techinical challenge of epiretinal implants
requires more data processing than subretinal implant (images must be processed into stimulation patterns that reflect retinal coding)
what is a bad thing about electrical retinal implants in general
require external power
can be uncomfortable and heavy for patient
what are optoelectronic implants
systems involving direct conversion of energy from light to electricity via photovoltaic components
much more promising
what is a photovoltaic subretinal prosthesis
- images from video camera processed by pocket PC and displayed on augmented-reality glasses
- images are projected from microdisplay onto photovoltaic cells with near-infrared pulsed light, generating electric current pulses in each pixel
- currents stimulate adjacent inner retinal neurons, providing visual information onto retinal network
what are advantages of photovoltaic subretinal prosthesis
thousands of photovoltaic cells (pixels) are activated simultaneously
pixels operate independantly of each other (no need for physical connection)
introduced by simple surgery into subretinal space as small, separate assemblies to tile large areas of visual field
what can optogenetics be used to do
stimulate surviving cells with light
outline optogenetics on the eye
genetic engineering of retinal neurons to become light-activated cationic channels (channel rhodopsin - blue light sensitive)
depolarize and fire upon exposure to blue light
outline the first positive trial of optogenetics
patient with retinitis pigmentosa - partial sight recovery following insertion of optogenetic sensor (ChrimsonR) in retinal ganglion cell
what is the link between saffron and eyes
saffron protects photoreceptors from dying
shown in albino rat study in their retinas,
exposed them to strong light for 24 hours, ones who ate saffron had less photoreceptor death than control
what is another study which shows the effectiveness of saffronn
in age-related macular degenration patients three months of exposure to saffron improved visual performance
took pills with saffron - 20mg a day
stabilised disease
why is saffron good for photoreceptors?
contains 30 active ingredients involved in prevention of photoreceptor degeneration
prevents:
oxidative stress, inflammation, apoptosis, hyperactivity of cellular matrix metalloproteases involved in neural remodelling
what is photobiomodulation
irradiation with light wavelengths from far red 600nm to infrared 1000nm has benefit in mammalian tissue
what is 670nm light thought to do
direct effect on cytochrome c oxidase (mitochondrial enzyme)
increase cytochrome c oxidase along with energy production in form of ATP
so:
= stimulates signalling pathways to improve mtiochondrial energy metabolism, antioxidant production and cell survival
what was 670nm light shown to alleviate in mouse retina
hyperoxia-induced degeneration
what are some other therpeutic approaches
stem cells - promising
gene replacement therapy
cell transplantation
