opto1001 week 7

biochemistry of vision

over how many log units of light intensity does human vision operate

approximately 10 log units

how much of the range of light intensity is accounted for by pupil size changes

approximately 1.2 log units

what is the role of pupil response in light adaptation

provides a dynamic shift while slower adaptation mechanisms activate

how fast is the pupil’s initial adjustment to light

0.2-0.5 milliseconds

what are the three types of visual modes

scotopic, mesopic and photopic

what type of vision is photopic and which photoreceptor are involved

daylight and cone driven

what type of vision is scotopic and which photoreceptor are involved

nighttime and rod driven

what are the characteristics of photopic vision

low gain and sensitivity, high spatial and temporal resolution

what are the characteristics of scotopic vision

high gain and sensitivity, poor spatial and temporal resolution

what type of vision occurs in dusk or moonlight and what photoreceptors are involved

mesopic vision with mixed rod and cone input

why do rods have a numerical advantage over cones

they outnumber cones by 20 to 1 which increases the chance of photon capture

how does convergence enhance rod sensitivity

multiple rods send signals to the same ganglion cell

how many isomerisations are needed to trigger a ganglion cell

about five

what are the two components of a visual pigment

chromophore (retinal) and opsin (protein)

what is retinal derived from and what does it absorb when free

retinal is a vitamin a1 aldehyde and absorbs 380nm when unbound

how does opsin affect retinal absorption

binding to opsin shifts absorption to longer wavelengths

what is the structure of opsin

350-450 amino acid chain that crosses the membrane 7 times as helices

what is bleaching in phototransduction

photon absorption converts 11-cis retinal to all-trans retinal causing it to seperate from opsin

what is the active form of rhodopsin and what does it do

metarhodopsin II (Rh*) and it initiates the phototransduction casade

how is Rh* deactivated

phosphorylated by rhodopsin kinase and bound by arrestin

what is the membrane potential of rods in darkness

appriximately 40mV

what maintains the dark current in rods

continuous influx of Na+ and Ca2+ through cGMP-gated channels

what neurotransmitter is continuously released by rods in darkness

glutamate

what regulates phototransduction readiness in the dark

calcium influx and high intracellular cGMP levels

what happens to retinal when a photon is absorbed

11-cis retinal converts to all-trans retinal

what does Rh* do first

activates transducin

what does transducin do after activation

exchanges GDP for GTP and activates PDE6

what is the role of PDE6 in phototransduction

hydrolyses cGMP to 5’-GMP which lowers cGMP levels

what happens when cGMP levels drop

cGMP channels close leading to membrane hyperpolarisation and reduced glutamate release

what is the peak absorption wavelength of rhodopsin

approximately 500nm

how quickly does rhodopsin activate after photon absorption

within microseconds

what activates transducin in rod phototransduction

Rh*

what molecular change occurs in transducin’s a-subunit

GDP is exchanged for GTP

what happens after the a-subunit is activated

dissociates from B and y-subunits and activates PDE6

what does PDE6 do

hydrolyses cGMP into 5’ GMP which lowers cytoplasmic cGMP levels

what is the effect of reduced cGMP on ion channels

cGMP-gated channels close which reduces Na+ and Ca2+ influx

what is the result of channel closure on membrane potential

membrane hyperpolarises which makes the potential more negative

how does hyper polarisation affect neurotransmitter release

glutamate release decreases

what happens after glutamate release decrease

signal is transmitted to downstream neurons

how many transducin molecules can one Rh* activate

hundreds

how many PDE6 molecules does each transducin activate

one and it amplifies the signal.

how many cGMP molecules does each PDE6 hydrolyse

hundreds to thousands

what is the result of cGMP hydrolysis on ion channels

closure of hundreds of ion channels

how many molecular events can one photon trigger

millions

how is Rh* deactivated

phosphorylation via rhodopsin kinase and binding by arrestin

how is transducin inactivated

hydrolysis GTP to GDP and reassociates with By-subunits

how is the calcium removed from the cell

via the Na+/Ca2+ exchanger

what does reduced intracellular Ca2+ activate

guanylyl cyclase which restores cGMP levels

what is the final outcome of termination

reestablishment of the dark current

what are the two phases of dark adaptation

rapid cone adaptation (first 5-10 minutes) and slower rod adaptation (20-40 minutes)

what is the rod-cone break

the point (approximately 5-10 minutes after light offset) when rod sensitivity overtakes cone sensitivity

how much more sensitive do rods become by the end of dark adaptation

10,000 to 100,000 times more 

what happens during rhodopsin bleaching

11-cis retinal converts to all-trans retinal after photon absorption

where does rhodopsin regeneration occur

RPE

what enzyme converts all-trans retinal to all-trans retinol

retinol dehydrogenase

what protein transports retinoids between photoreceptors and RPE

interphotoreceptor retinoid-binding protein (IRBP)

what does LRAT do in the RPE

esterifies all-trans retinol into retinyl esters

what enzyme converts 11-cis retinol into 11-cis retinal

11-cis-retinol dehygrogenase

what stabilises 11-cis retinal in the RPE

CRALBP

what happens after 11-cis retinal returns to photoreceptors

recombines with opsin to regenerate rhodopsin

what activates guanylyl cyclase during dark adaptation

reduced intracellular calcium

what does guanylyl cyclase do

increase cGMP synthesis to reopen ion channels

how does rhodopsin sensitivity increase during adaptation

dephosphorylation and arrestin dissociated

what structural changes optimise in phototransduction

disc membrane reorganisation and protein redistribution

how is dark adaptation clinically assessed

dark adaptometry

what conditions may impair dark adaptation

vitamin a deficiency, retinitis pigments and AMD

how does age affect dark adaptation

older individuals adapt more slowly

why is nutrition important for dark adaptation

vitamin a is essential for regenerating visual pigments

what trigger depolarisation in ON bipolar cells

increase in light which causes decrease in glutamate release

what trigger depolarisation in OFF bipolar cells

decrease in light which cases an increase in glutamate release

what do ON and OFF pathways help encode

brightness and dimness in visual signal

what happens to all-trans retinal in the photoreceptor outer segment

dissociates from opsin and is reduced to all-trans retinol by retinol dehydrogenase

what protein transports retinol to the RPE

IRBP

what does CRBP do in the RPE

binds all-trans retinol for processing 

what is the role of LRAT in the visual cycle

esterifies retinol into retinyl esters

what enzyme converts retinyl esters into 11-cis retinol

RPE65

what converts 11-cis retinol into 11-cis retinal

11-cis-retinol dehydrogenase

what stabilises 11-cis retinal before it returns to photoreceptors

CRALBP

what happens when 11-cis retinal returns to photoreceptors

recombines with opsin to regenerate rhodopsin

what condition is caused by RPE65 mutations

Leber congenital amaurosis

what condition is associated with LRAT deficiency

early-onset severe retinal dystrophy

what do visual cycle defects commonly lead to

inherited retinal diseases

what are G proteins and what do they regulate

molecular switches that regulate intracellular signalling

what are the two main types of G proteins

heterotrimeric and monomeric

what are the three subunits of heterotrimeric G proteins

a, B and y

what do GAPs do

accelerate GTP hydrolysis to shorten signal duration