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Describe Joan's case.

- 45 year old woman
- has trouble seeing at night
- trips over her children's toys
- has had many car accidents over the last 2 years
- can read OK
- black crud in peripheral retina - indicative of a disease process in the retina
- pigment that has come from underneath
- macula is fine so has no central vision problems
- has tunnel vision


What is the anatomy of the eyeball?

- cornea at the front - clear surface that light passes through
- lens bends the light
- focussed on the retina which occupies the back sort of 5/6 of the eyeball (inside surface of the eyeball)
- outer layer is there for strength
- middle layer with lots of blood vessels for nutrition
- inner layer = retina
- optic nerve contains the axons of the ganglion cells as they go off to the brain
- fovea is the most important part of the eye - allows us to see centrally


What fundamentally limits visual acuity?

1. neural factors
2. optical factors


What are optical factors affecting visual acuity?

- pupil size
- clarity of optical media: cataracts, corneal opacities etc
- refractive errors --> blur: myopia, hypermetropia, astigmatism, presbyopia


Describe the neural retina

- a series of neurons and neuronal layers
- light has to go all the way through the retina to the photoreceptors which sit very deep in the wall of the eyeball
- the photoreceptors are the cells which 'see' the light and stimulate a neural response
- pigmented epithelium lay behind the photoreceptor cells and help keep the photoreceptors alive
- if the retina was layered the other way around the pigmented cells would be the first thing the light reached: these cells prevent light from passing through


What are the photoreceptor cells?

- night vision
- "scotopic"
- very sensitive
- one type only
- no colour vision
- 100 million
- absent from fovea

- day vision
- "photopic"
- less sensitive
- three types
- allow colour vision
- 5 million
- densest in fovea


How do we optimise our ability to see?

- cone and rod density changes
- cones are extremely dense in the middle of the fovea whereas rods are lowest
- fine detail during the day is defined by cones
- rods are more dense in the periphery


How do photoreceptors function?

- two important things needed for phototransduction: photopigment and retinal
- photoreceptors contain photopigments that are activated by light
- rods contain Rhodopsin
- cones contain one of three different coneopsins
- opsins bind to vitamin A (all-trans Retinal)

- in the dark retinal is kinked and does not activate rhodopsin, thus allowing a continuous influx of sodium ions through a cGMP gated sodium channel: this depolarises the cell
- Retinal picks up the up the light, changes and then changes the rhodopsin protein (activates it)
- initiates a cascade of events that ultimately leads to the closure of cGMP gated sodium channels and prevents the flow of sodium ions
- Rh --> transducin --> PDE (phosphodiesterase) --> breaks down cGMP
- closure of sodium channels --> hyperpolarisation

- respond to light with graded changes in membrane potential (not action potentials)
- continuous release of neurotransmitter that goes down when hyperpolarised, or up if the cell is slightly depolarised


What is the structure of a Rod?

- outer segments = contains the proteins that are sensitive to light
- cell body
- axon and synaptic terminals


How does the structure of retinal change when hit by light?

- retinal usually in 11-cis retinal form - kinked
- when light hits it, it becomes unkinked and straight forming All-trans retinal form
- this gets the whole process going


What is the neurotransmitter in rods?



How is the retina wired up?

"Through" pathway:
- Photoreceptors
- Bipolar cells
- Ganglion cells

Lateral interactions:
- horizontal cells (outer retina - modify signal)
- amacrine cells (inner retina - modify signal)


What are second order neurons?

- bipolar cells
- important in "through"
- 10 different types:
-- 1x rod bipolar cell
-- 9x cone-bipolar cells
- important for spatial vision, and colour vision
- found in the inner nuclear layer (second layer)


What are ganglion cells?

- output neurons of the retina
- many different types: On, Off, M (motion) and P (important for how we see colour) (maybe 22 different types)
- release glutamate
- fire action potentials


What are the receptive field properties of ganglia? How does this allow ganglion cells to integrate information over time?

- ganglion cells respond to light by either increasing or decreasing their action potential firing rate
- receptive field of a ganglion cell: is the area of retina that when stimulated with light changes the cell's membrane potential
- allows us to pick up edges
- response of a ganglion cell can vary over time:
-- transient: sudden burst of APs at the onset of stimulus (i.e. transient)
-- sustained: continuous APs during stimulation
- GCs are especially tuned for edges


How do ganglion cells convey parallel information?

- 20 different types of GCs
- ganglion cell responses:
-- increase or decrease in firing
-- transient or sustained response
- visual information is passed to higher cortical centres in parallel
- ganglion cells deconstruct what we see and the brain puts it all back together


What is lateral inhibition?

horizontal cells
- input from photoreceptors
- provide output onto photoreceptors
- use inhibitory neurotransmitter GABA
- respond to light by hyperpolarising
- this is what develops the receptor field property in ganglion cells

amacrine cells
- many different types
- axonless cells
- important for lateral inhibition
- for the most part ACs are considered inhibitory cells (release inhibitory NTs: glycine, GABA)


So what's wrong with Joan?

Retinitis pigmentosa
- 1:5000
- genetic defect in rhodopsin, or proteins involved in phototransduction (around 150 different mutations in rhodopsin)
- tunnel vision
- has a field of the order that's about 5º
- eventually causes blindness