S3: Visual Physiology Flashcards
Describe structure of cone receptors
- The specialised bit of the cell is the outer segment. It consists of stacks of phospholipid bound sacks. The function of these stacks of membrane is for holding in place metabolites (phototransduction is a biochemical reaction that requires enzymes, proteins etc if which many are membrane bound).
- The inner segment contains a nucleus, axon and synaptic terminal that releases glutamate (fast excitatory NT). The ‘axon’ does not fire any AP as it is too small.
Describe the mechanism of cone receptors in response to increased light (using RMP)
- Remember that photoreceptors are nerve cells that come from the neural tube.
- Therefore, photoreceptors have K+ leak channels and this gives it a negative RMP as K+ leaks out.
- However, the membrane potential is not as negative as in a normal nerve cell and it is more positive at about -45mV. This is because the outer segment has Na+ channels that allow Na + to leak into the cell, adding positive charge making the RMP more depolarised then normal.
- This means the photoreceptor has a intermediate position RMP where it can depolarise or hyperpolarise quite strongly (remember it can’t fire any AP).
- When the amount of light (illlumination) hitting the outer segment increases, some of the Na+ channels close shut which stop much of Na+ going into the cell while K+ continues to leak out.
- This results in the cell hyperpolarising which causes a reduction in the release of glutamate.
Describe the mechanism of cone receptors in response to decreased light and how the photoreceptors will respond as an individual looks around the room
- When the amount of illumination hitting the retina decreases, there then will be more Na+ open, causing more Na+ flow into the cell causing a depolarisation. This will result in increased release of glutamate.
- As the person looks around the room, the photoreceptor will switch between hyperpolarising and depolarising as illumination decreases and increases. It is equally sensitive to both increase and decrease of light.
List steps on transduction (how illumination closes/opens Na+ channels and changes how much glutamate released)
- Initiation of light response.
- Amplifying biochemical cascade.
- Termination of the response.
This all occurs in response to one photon but in reality we have lots of photons hitting our retina so this will be happening over again.
Explain transduction: initiation of the light response (photoisomerisation of retinal)
- Embedded in one of the membrane discs in the outer segment of the photoreceptor, is a protein called opsin.
- The opsin has a binding site for a molecule of retinal (chromoform). The retinal is the area that detects the light and together, the opsin and retinal form the photopigment.
- The retinal when bound to opsin and ready to be activated is called the 11-cis retinal because of its chemical structure. All the carbon bonds are trans bonds except the one at the 11th carbon which is a cis bond and this is a relatively weak bond and a kink in the tail of retinal.
- Hence when a photon of light hits the it, the cis bond breaks and when it reforms, it becomes a trans bond which is more stable creating all-trans retinal.
- This photoisomerisation of retinal is the light sensitive step.
- The sodium channels at this point, are held open by two molecules of cyclic GMP which are intracellular messengers.
Explain transduction: amplifying biochemical cascade
- At this point, there is activated photopigment which triggers an amplifying biochemical cascade (activating G protein which activates an enzyme) resulting in cGMP to be broken down and its concentration intracellularly to decerease.
- The active opsin, can activate many G protein switch will activate many enzymes.
- The Na+ channels in the outer segment are held open by cGMP so a fall in cGMP will cause some channels to close.
- This is why increased illumination causes decreased Na+ movement into the cell and hyperpolarisation.
Describe transduction: termination of the response
- There is the need for the response to be terminated as we don’t want transduction to be going on continuously in photoreceptor.
- A process occurs where the trans retinal is taken away to the retinal pigment epithelium (RPE) and glial cells to be converted back to 11-cis retinal.
- The opsin is now inactivated so the biochemical cascade stops and a new enzyme comes in and replenished levels of cGMP so the Na+ channels reopen.
- The 11-cis retinal is then put back into the opsin creating a new photopigment ready to respond.
Describe adaptation of our cone photoreceptors
- Our cones need to give us strong responses even to minute changes in brightness. So they need to constantly adapt by resetting sensitivity of amplification cascade (by either opening or closing sodium channels to bring membrane potential down to RMP. This occurs due to continuous stimulation that doesn’t change.
- They control the rate and sensitivity
What is retinitis pigmentosa?
- Defects in many of the necessary proteins result in degenerative disease as the whole transduction process is very complex.
- Retinitis pigmentosa is when there is degeneration from ouside inwards of the retina.
- It is generally driven by a mutation in one of the rod enzymes or proteins and it starts with degeneration of rods and then eventually the entire retinal circuit.
What is the result of our photoreceptor outer segments producing a very fast response to light?
- We can see a stimulus that is flickering 70 times per second.
- This results in a very high metabolic rate and response so they need a very rapid supply of oxygen and nutrients.
- Photoreceptors use GTP and ATP very rapidly.
- This is usually delivered by a dense capillary bed but this is not possible in the outer layer of the retina as it would block the light path
- A solution is the choriod.
What is the result of our photoreceptors being packed tightly together?
- Photoreceptor outer segments support high resolution sampling of the visual image by being packed tightly together.
- This is not possible with a normal capillary bed so the choriod is the solution.
Describe how our photoreceptors have a highly specialised blood supply
- The highly metabolic outer segments of the photoreceptors lay just under the renal pigment epithelium which is a single layer of cuboid cells.
- Surrounding the pigment epithelium on the outside is the choroid blood supply.
- The choroid is a massive blood supply and so efficient and rapid at carrying oxygen to the photoreceptor outer segments so that they are constantly in an environment of arterial partial pressure despite the fact they are constantly using it up and converting it to CO2.
- This is why the outer segments must lay near the choroid because it is the only way of supplying their demand for oxygen explaining why the retina is ‘inside out’ and why outer segments are pointing away from the light.
Describe how the retinal pigment epithelium (RPE) sits between the photoreceptors & the choroid
- The renal epithelium cells surround the photoreceptors.
- The pigment epithelial cells create sheets that project in between the outer segments (interdigitates),
- The only thing holding the photoreceptors to the RPE is the fact the pigment epithelial cells are sucking fluid out of the gaps in between. This suctioning keeps the retina in place (holding neural retina onto pigment epithelium). This is why if there is a break in the retina that allows fluid to flow into that space faster than the RPE can remove it, then the retina will peel away from the RPE and this is a detached retina.
- Hence one of the functions of the RPE is to hold the retina in place.
Describe function of retinal pigment epithelium (RPE)
- The RPE cells act as the blood-retinal barrier between outer sements and the choroid. It has tight junctions and control the flow of substances in and out of the retinal tissue. They allowing nutrients in and waste out.
- It will also take the trans-retinal (activated) and convert it to 11-cis retinal which can then be returned back to the photoreceptor.
- It also renews the outer segment membranes of cone photoreceptors. RPE cells act as phagocytic cells and bite the top of the outer segments of photoreceptors, the outer segments then regrow. This is due to photooxidation of lipids and proteins that can occur to the outer segments due to light and this can build up damage molecules.
In this way every 10 days the outer segments are replaced. - It holds the retina in place.
- Also contains pigment granules that absorb stray light.
How can RPE be damaged?
- Degeneration of RPE is a feature of many retinal diseases.
- Retinoids are molecules that can damage cell membranes, usually they will be chaperoned around to prevent this, but sometimes this can go wrong and cause damage!
- The outer segments and RPE are subject to high oxygen concentration as well as electromagnetic radiation (light!), these combined can cause photo-oxidation. Unfortunately it is phospholipids and proteins (the very substances that the outer segments are made of) that are easily oxidised. This is partly why the outer segments must be replaced regularly, in order to remove damage regions.
How can ‘drusen’ occur?
- If damaged parts of the outer segments on photoreceptors are not removed, the damaged molecules tend to hang around.
- With age, the RPE tends to become clogged with intracellular debris (called lipofusin). Some of this comes from photo-oxidised proteins and phospholipids of retinal image.
- It seems the RPE gets rid of some of this debris by depositing it onto the basement membrane, where it attracts cholesterol and immune cells from the blood which builds up fatty plaques (called drusen). This is because damaged lipids and proteins can’t be digested by RPE.
- Where there is drusen, there is likely to be death of photoreceptors as they are blocking movement of oxygen and nutrients from the blood. This is partly why vision decreases as we age, as the photoreceptors are being killed off in this way.
What are the ganglion cells in the retina?
- The ganglion cells are the afferents of the system. They are linked to the photoreceptors by bipolar cells.
- Each cone photoreceptors (of which there is only one array) will provide input to one of several populations of ganglion cell.
List the 4 types of ganglion cells
- ‘Off’ cells.
- ‘On’ cells.
- ‘Parvocellular’ cells.
- ‘Magnocellular’ cells.
Describe ‘off’ and ‘on’ ganglion cells
- ‘Off’ cells are excited by decreased illumination of their photoreceptors over their receptive fields.
- ‘On’ cells are excited by increased illumination of their photoreceptors.
- This is interesting because despite the photoreceptor itself hyper-polarising and having reduced firing on increased illumination, some ganglion cells will be excited.
- So although all photoreceptors will be depolarised by decreased illumination, this is only true for half of the ganglion cells, the other half are excited when light falling on their receptive field increases.
What is the fuction of parvocellular ganglion cells?
- These are specialise for high resolution and colour (have small receptive fields so input is from one or two cones),
- They extract fine detail and colour information.
- They only work well when image is stable as they are insensitive (if image is moving these GC don’t work well).
What is the function of magnocellular ganglion cells?
- These are specialised to detect fast moving objects and low contrast objects (broad outlines).
- They receive input from many cones and rods.
Describe mechanism of parvocellular ganglion cells for fine detail using the parvocellular receptive field
- The parvocellular ganglion cells which are involved in the pathway for fine detail have very small receptive fields with one or two cones.
- If just this central receptive field experiences a change in illumination, then the ganglion cell will respond.
- However, the get fine responses, as well as a small receptive field, there needs to be lateral inhibition of surrounding areas.
- If the yellow ganglion cell has change in illumination just in its central receptive field, then the inhibitory interneurons will be activated by the corresponding cone and inhibit the surrounding cones. This enhances and pin points the visual information seen by that ganglion cell and allows fine detail.
- Alternatively if there is illumination of a wider area, covering the receptive field and surrounding area then the retinal ganglion cell will get inhibited by the interneurons due to activation of surrounding cones.
Describe how retinal ganglion cells respond to contrast between the illumination of centre and surround
- A parvocellular ganglion cell will only fire when there is excitation in the centre of its receptive field and not fire if it and its surroundings are excited to an equal extent because the inhibition and excitation will cancel out.
- Thus parvo ganglion cells only respond to contrast and thus allow us to see edges. This is because where a ganglion receptive field is on the edge, it is receiving different information to the surrounding and therefore will be excited (the brain will recognise this specific response and allow us to see edges).
- The ganglion cells receptive fields that cross the edge will be receiving different levels of brightness and info coming in from the visual world. Hence the photoreceptors will be activated differently and the inhibition will not cancel out everything, rather the ganglion cell will be activated and the brain recognises this information as meaning an edge.
How does our brains get confused when retinal ganglion cells respond to contrast between the illumination of centre and surround? (with example)
We witness this in optical illusions.
This is because our brain is enhancing the edges, telling us that the bar is brighter against the dark background and darker against the white background.
The brain isn’t getting information about the centre of the bar, so it interprets it as being shaded.