Lecture 11: Sight and blue tinted vision Flashcards
Tuesday 4th February 2025
What is visual perception mediated by?
Visual perception is mediated by specialised GPCRs (G-protein-coupled receptors) that detect light and initiate complex signalling cascades in the retina. The key players are rod and cone cells.
What are rod cells responsible for?
Responsible for monochromatic vision at low light intensities.
What are cone cells responsible for?
Responsible for colour vision at higher light intensities.
Describe the anatomy of photoreceptor cells
- Light travels through the neural retina before reaching photoreceptors.
- Outer segment: Consists of ~1000 disc-like structures containing rhodopsin.
- The structure is derived from a primary cilium, acting as a sensory organelle.
Describe rhodopsin
- Rhodopsin is a GPCR bound to a chromophore called 11-cis-retinal, which absorbs light.
- Retinal is covalently linked to lysine 296 on transmembrane domain 7.
Describe the light activation process in rhodopsin
- cis → trans isomerisation of 11-cis-retinal occurs upon light absorption.
- This shifts the position of the lysine-attached nitrogen by ~0.5 nm.
- Causes a conformational change → activates rhodopsin into metarhodopsin II.
What are the key players in the GPCR signalling cascade in rod cells?
- Rhodopsin (activated GPCR)
- Transducin (Gt): A specialised heterotrimeric G-protein
- cGMP phosphodiesterase (PDE6)
What are the signalling steps for rhodopsin?
- Light → activates rhodopsin.
- Rhodopsin activates transducin (GDP → GTP exchange on α-subunit).
- Gαt (transducin α-subunit) activates PDE6.
- PDE6 hydrolyses cGMP to GMP.
- Reduced cGMP causes closure of cGMP-gated Na⁺/Ca²⁺ channels.
- Membrane becomes hyperpolarised (from ~−40 mV to −70 mV).
- Result: Light is converted into an electrical signal.
How sensitive is rhodopsin?
- Very sensistive
How is rhosopsin sensitive?
- A single photon can activate rhodopsin.
- ~5 activated receptors can produce a visible flash.
- High sensitivity makes rods effective under dim conditions.
Explain the desensitisation mechanisms of rod cells
1) Ca²⁺ levels drop due to channel closure → activates guanylate cyclase → replenishes cGMP → channels reopen.
2) Rhodopsin phosphorylation (up to 7 sites) by rhodopsin kinase reduces its activity.
3) Arrestin binds phosphorylated rhodopsin → halts transducin activation.
Describe signal amplification in rod phototransduction
1) One rhodopsin → activates ~500 transducins
2) → activates ~500 PDE6 molecules
3) → hydrolyses ~10⁵ cGMP molecules
4) → closes ~100–250 Na⁺ channels
5) → prevents entry of ~10⁷ Na⁺ ions
6) → triggers significant membrane hyperpolarisation
What makes humans trichromats?
- They have 3 cone types:
- S-cones: 414–426 nm (blue)
- M-cones: 530–532 nm (green)
- L-cones: 560–563 nm (yellow-red)
Compare cones to rods
- Cones have the same structure as rods (opsin + 11-cis-retinal), but different amino acid sequences in opsin tune sensitivity to different wavelengths.
- Different transducins are used for cone signalling.
Describe the vision of mice
dichromatic (~510 nm green, ~350 nm UV)
Describe the vision of birds
tetrachromatic or pentachromatic; some are UV-sensitive
Describe the vision of Cichlid fish
up to 7 pigments (heptachromats)
Describe the vision of Mantis shrimp
12+ receptors, including those for polarised light
Describe Cephalopods and Chromatic Aberration Detection
- Octopuses, squids have only rod cells, yet change skin colour effectively.
- Use chromatic aberration (light diffraction) processed by large optic lobes to detect colours indirectly.
- Their weird pupils (U-, W-, dumbbell-shaped) accentuate diffraction, giving colour info.
Is it true that most humans are trichromats?
Yes
Is it true that dichromats lack one cone type?
Yes
Anomalous trichromats..
shifted spectral sensitivity.
Is it true that some females are tetrachromats?
Yes (extra cone type via X-chromosome)
Historical Case: John Dalton
- Famous chemist and colour-blind individual.
- Thought he had blue-tinted eye fluids.
- 1995 genetic analysis confirmed he was a deuteranope (missing M-cone opsin gene).
Evolutionary Pressures on Colour Vision
- Peak cone sensitivities may reflect trade-offs:
High yellow-orange resolution → reduced spatial resolution
- High spatial resolution in blue → lower colour sensitivity
- Hypothesis: Ripe fruit selection may have driven trichromacy in primates.
- Dichromats may excel at spotting camouflaged objects (e.g., 1940 Oklahoma study).
What is Sildenafil (Viagra)?
A PDE5 inhibitor, also inhibits PDE6, affecting vision.
What are the side effects of Sildenafil?
blue-tinged vision (due to altered cGMP levels in cones).
What is teh FAA warning agasinst SIldenafil?
pilots should avoid flying for 6 hours after taking it — affects ability to distinguish cockpit lights.
Summary and Takeaways
- Visual transduction is a highly efficient, amplified, and reversible GPCR signalling system.
- Rods = extreme sensitivity, cones = colour discrimination.
- Evolution has shaped a wide range of visual systems.
- Human trichromacy offers both advantages and trade-offs, and “colour blindness” may have unseen benefits.
What is the inner and outer segment of a photoreceptor cell?
A primary cilium (primary cilia extend from the surface of most vertebrate cells – and act as signalling organelles).
Where has light signalling been most extensively studied?
Light signalling has been most extensively studied in rod cells, responsible for non-colour vision at low light intensity.
Is it true that colour vision is provided by cone photoreceptor cells at high light intensity?
Yes
What does the outer segment of rods contain?
- The outer segment contains ~1000 discs, not connected to the plasma membrane.
- Each is a closed sac of membrane with embedded photosensitive rhodopsin molecules.
Is it true that light energy can be converted into atomic motion within a few picoseconds?
Yes
What does Metarhodopsin stimulate?
Metarhodopsin stimulates nucleotide exchange on the α-subunit of a specific heterotrimeric G protein called transducin (Gt).
Is it true that there are multiple heterotrimeric G-proteins?
Yes
What does Gαt (GTP) stimulate?
Gαt (GTP) stimulates cGMP phosphodiesterase (cGMP PDE) which removes cGMP from cGMP-gated ion channels.
ions can’t enter membrane and membrane becomes more negative/ depolarised).
Is it true that light closes the cGMP gated ion channels, reducing the influx of Ca2+?
Yes
What happens when low Ca2+ levels are detected in rod cells?
- guanylate cyclase is activated
- cGMP levels rise
- channels re-open – ready to be closed gain by light.
Under high light intensity, rod cells are inhibited, and less sensitive to small changes in light intensity.
Under high light intensity, rod cells are inhibited, and less sensitive to small changes in light intensity.
Which 3 mechanisms makes rods insensitive to high light?
① Prolonged cGMP-gated channel closure
② Phosphorylation of opsin reduces transducin activation
③ Arrestin binding to phosphorylated opsin stops transducin activation
is cGMP a second messenger?
Yes
What does the cis →trans isomerisation of retinal converts light energy into?
atomic motion, activating rhodopsin. 1 receptor stimulated.
What makes pigeons pentachromic?
The fact that they have an additional pigment to most other birds.
Describe the colour receptors of mantis shrimps
12 receptors for colour sensitivity; others for intensity and polarization (perhaps 20 in total).
What does the retina use to capture light?
cis-trans isomerisation
What is the key structure for light reception?
The retina is the key structure responsible for light reception, containing specialized photoreceptor cells (rods and cones).
What is the cornea?
The transparent front part of the eye that helps focus incoming light.
What does the lens do?
Adjusts shape to focus light onto the retina.
What is the retina?
A thin layer of tissue at the back of the eye where light is detected.
What does the optic nerve do?
Transmits visual signals to the brain.
What is the Vitreous Humor?
Gel-like substance filling the eye, maintaining shape.
💡 Key Concept: Light must pass through multiple layers of the retina before reaching the outer segments of rods and cones, where phototransduction begins.
💡 Key Concept: Light must pass through multiple layers of the retina before reaching the outer segments of rods and cones, where phototransduction begins.
What is the peak of sensitivity of mammalian rhodopsin?
500 nm
Describe the difference between a Cephalopod and a human eye
- In a Cephalopod: light strikes the retina directly, there is no blind spot, the retina has only rod cells.
- In a human eye: Light strikes the retina indirectly, there is a blind spot, the retina has rods and cones.
What is interesting about the pupils of octopi?
- U-shaped, W-shaped or dumbbell-shaped.
- They allow light to enter the eye through the lens from many directions at the same time, rather than just straight into the retina.
What is fascinating about octopi?
They only have rods and no colour receptors, but can somehow still change colour.
Our eyes/pupils…
- Our round pupils can contract to give us sharp vision, with all colours focused on the same spot.
- If our pupils dilate we see coloured fringes around objects - chromatic aberration, caused by light diffraction.
- The larger the pupil the greater the chromatic aberration.
The pupils of octopi…
- Cephalopods have wide pupils that accentuate chromatic aberration.
- Cephalopods have large optic lobes in their brains: they can process chromatic diffraction.
- They change the depth of their eyeball, altering the distance between the lens and the retina, and moving the pupil around to change its off-axis location and thus alter the amount of chromatic blur.
- These ‘colour-blind’ animals can process light diffraction and so they can ‘see’ colour! Amazing.
- Those large optic lobes… …are required to process all those diffraction data.
Is there a selective pressure for us to maintain two visual pigments with close peak frequencies?
Yes
What issues do dichromats have?
Dichromats have difficulty distinguishing similarly sized objects where lightness varies in an unpredictable manner
What conclusion did testing Dalton’s eyes lead to?
CONCLUSION: Dalton had a deletion of the gene encoding the MW (green) visual pigment. He was a genetic dichromat: a deuteranope.
Is it rue that dichromats tends to see camoflage more quickly than trichromats?
Yes, and this may provide a rationale for why colour blindness is maintained in the population.
What is a potent competitive inhibitor of cGMP phosphodiesterase?
Sildenafil. It is most active against phosphodiesterase type 5 (PDE-5). Sildenafil citrate also inhibits PDE-6. PDE-6 regulates blue-green colour discrimination in the retina
