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Optometry Class OP4102 > The Retina > Flashcards

The Retina Flashcards

1
Q

why is the optic disk a blindspot?

A

as there are no photoreceptors in that area

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2
Q

what is the macula lutea?

A

a yellow spot on the retina that’s due to an accumulation of retinal carotenoids

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3
Q

give the 11 layers of the retina

A
  1. ILM: inner limiting membrane
  2. NFL: nerve fibre layer
  3. GCL: ganglion cell layer
  4. IPL: inner plexiform layer
  5. INL: inner nuclear layer
  6. OPL: outer plexiform layer
  7. ONL: outer nuclear layer
  8. OLM: outer limiting membrane
  9. is: photoreceptors innersegments
  10. os: photoreceptors outersegments
  11. RPE: retinal pigmentepithelium

If Nans Go In Iceland Or Other Outings Phone Papa Really

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4
Q

what are the three neurones in the retina?

A
  1. ganglion cells
  2. bipolar cells
  3. photoreceptor cells
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5
Q

What are the features of the internal limiting membrane?

A

-mainly composed of basement membrane formed by muller cell footplate processes
-occasionally astrocyte processes and consist of broad flat cells containing rod shaped nuclei
-ILM has the vitreous attached through fine collagen fibrils
-normally absent over the optic nerve head

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6
Q

what are the layers of the ganglion of the ILM?

A

-Nerve fibre layer - Axons of retinal ganglion cells -(RGCs)+ a few neuroglial cells (astrocytes =astroglia and microglia)
-Ganglion Cell Layer- Retinal ganglion cell (RGC)bodies and some amacrine cell bodies Inner
-Plexiform Layer- Axons and dendrites: synapses of bipolar cells and amacrine cells with ganglion cells

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7
Q

what are the layers of the bipolar layer of the ILM?

A

-inner nuclear layer: consists of the cell bodies of nueornes (amacrine, bipolar and horizontal cells) and muller cells
-outer plexiform layer: synapses of photoreceptor cells with bipolar and horizontal cells

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8
Q

what are the layers of the photoreceptor layer of the ILM

A

-outer nuclear layer whicnb has 8-9 layers of of densly packed nuclei and cell bodies of the rods and cones but rods have smaller nucei while cones have larger nuclei that reside just internal to the external limiting membrane
-external outer limiting membrane (not an actual membrane) - where zonula and macula adherens connect muller cells with photoreceptor inner segments that connect muller cells with

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9
Q

describe the features of the inner segment of a photoreceptor

A

-it extends beyond the external limiting membrane
-ER for protein and lipid synthesis, golgi for carb synthesis and protien modification
-cone inner segment, larger than in rods and contains numerous mitochondria
-rod inner segment is cylindrical and fewer mitochondria than in cones

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10
Q

what do photoreceptor cilia consist of? what are they for? when are they dysfunctional?

A

-inner and outer segment connected by a modified cilium
-nine doublet microtubules with no central microtubules
-important in transfer of molecules
-often dysfunctional in ushers syndrome

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11
Q

what are the two parts of the photoreceptor outer segments and what do they consist of?

A

-Rod OS: stacked disks separated from the plasma membrane
-Cone OS stacked disks continuous with the plasma membrane

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12
Q

give four features of rod disks in the outer segment

A

-contains 600-1000 stacked disks
-connected to plasma membrane but its not continuous with it
-2 micrometers in diameter
-rhodopsin molecules are located within disc membranes

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13
Q

what two types of epithelium does the RPE consist of?

A

-simple cuboidal epithelium: a monolayer of regularly arranged hexagonal cells
-simple columnar epithelium over the fovea

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14
Q

how is the RPE highly polarised?

A

due to the zonulae occuludentes ( tight junctions )

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15
Q

whys the RPE so important?

A

provides the blood brain barrier

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16
Q

what are the cartenoids that comprise the macular pigment in the macula lutea?

A

carotenoids:
-meso zeaxanthin
-lutein
-zeaxanthin

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17
Q

what is the use of the macula lutea?

A

the macular pigment heightens absorption of blue light so enhances visual resolution

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18
Q

what does the central retina contain?

A

the macula which consists of
-fovea centralis
-foveola
-parafovea
-peri fovea
-optic disk

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19
Q

What does the apical surface of the RPE contain?

A

microvilli bathed in the interphotoreceptor matrix

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20
Q

what does the basal surface of the RPE contain?

A

infoldings at the basal surface that increase its surface area

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21
Q

give the steps in transport, synthesis, recycling, and storage in the rpe

A
  1. Diffusion/uptake of oxygen and nutrients from blood
  2. Uptake and storage of nutrients and micronutrients (including vitamin A), and their transformations
  3. Transport of nutrients and 11-cis-retinal to photoreceptors
  4. Regulating flow of water and other molecules by tight junctions (gate and fence function); providing the blood-retina barrier
  5. Phagocytosis of tips of photoreceptor outer segments(POS)
  6. Recycling of proteins, lipids, and vitamin A from phagocytosed and degraded POS
  7. Removal of waste products to the blood
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22
Q

what happens to the oxygen conc of cone cells in the dark

A

the oxygen concentration becomes close to zero in the inner segment layer as the oxygen use is very high in the dark

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23
Q

which inner segment between cones and rods contains more mitochondria?

A

cone inner segment and hence it has a larger inner segment than rods because in the dark, the cones have a high oxygen consumption so theres a constant need to receive oxygen and nutrients

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24
Q

give the cation channels in the outer segment of photoreceptors

A

-Na/ K, Ca exchanger
-cGMP - gated channel due to influx of Na+ and Ca+

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25
Q

give the cation channels in the inner segment of photoreceptors

A

-potassium channels
-ATP dependent Na-K pumps responsible for the constant circulation of ions in the dark

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26
Q

what are omega 3 lipids for in rod disks? what is it called?

A

-provides high fluidity to the lipid membrane as deficiency causes impairment of learning and memory
-docosahexaenoate (DHA)

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27
Q

what’s the difference in length between rod and cone cells?

A

rods have long outer segments that reach the RPE while cones have a shorter outer segment so send microvilli to encompass the cone outer segments

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28
Q

what happens in the phagocytosis of photoreceptor outer segments by the RPE in three steps

A
  1. disc shedding
  2. phagocytosis
  3. lysosomal degradation
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29
Q

in a sequence, how does the RPE have a role in providing 11-cis-retinal the chromophore of visual pigments? (retina 2 for relevence)

A
  1. uptake of vitamin A ( all trans retinol) from the blood
  2. uptake of vitamin a from the interphotoreceptor matrix
  3. intracellular transport of retinoids by the cellular retinoid binding protein and the cellular retinal binidng protein
  4. esterification of vitamin A with fatty acids by lecithin retinol acetyl transferase to form retinyl esters
  5. storage of retinyl esters
  6. synthesis of 11-cis retinal to form all trans retinyl esters
  7. transport of 11-cis-retinal to photoreceptor outer segments
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30
Q

why does the fundus appear as the darker area in the fovea?

A

due to increased melanin in the RPE

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31
Q

where is melanin synthesised?

A

in the protein matrix of melanosomes

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32
Q

which optic layer doesn’t disappear in the optic disk?

A

the nerve fibre layer

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33
Q

what does the fovea mainly consist of and what is the ratio of photoreceptors, bipolar and ganglion cells and why is it that?

A

Mainly cones with specialised architecture that resembles rods, 1:1:1 and this is to enhance the resolution of spatial and temporal simulation

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34
Q

what is the maximal retinal thickness?

A

349+- 17 micrometers

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35
Q

compare the number of cones and rod

A

rods:
78-125 million/ retina

cones:
5.6-6.8 million/retina

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36
Q

what part of the retina is the density of cones highest?

A

in the fovea

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37
Q

in what part of the retina is the density of cones the least?

A

temporal periphery side

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38
Q

what is the parafovea?

A

a 0.5mm ring surrounding the fovea and has the largest density of ganglion and bipolar cells

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39
Q

what is the perifovea?

A

a 1.5mm ring surrounding the parafovea with less ganglion cells than the parafovea

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40
Q

what is the peripheral retina?

A

a mostly single cell layer of ganglion cells outside the macula

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41
Q

Give a brief sequence of phototransduction in photoreceptor neurons in 3 steps

A
  1. absorption of a photon
  2. hyperpolarisation of plasma membrane
  3. release of the neurotransmitter of glutamate is inhibited
42
Q

watch the khan academy video on phototransduction in photoreceptors

A

ok

43
Q

give the sequence of events in the phototransduction cascade

A
  1. visual pigment is activated - rhodopsin in rods
  2. activation of transducin
  3. activation of phosphodiesterase (PDE)
  4. degredation of cGMP to GMP
  5. closure of cCMP gated channels
  6. Na+ decreases and Ca2+ decreases
    -plasma membrane is hyperpolarised
44
Q

how is the yield of photoactivation of rhodopsin very high?

A

every 2 out of 3 absorbed photons leads to photoactivation of rhodopsin

45
Q

what are rods and cones in terms of day and night vision?

A

rods: scotopic - night
cones: photopic - day

46
Q

in the phototransduction cascade at the end, how does the release of glutamate get inhibited?

A
  1. hyperpolarization of plasma membrane spreads to the synaptic terminal
  2. voltage-dependent Ca2+ channels in the synaptic terminal close
  3. the influx of Ca2+ is decreased
  4. this inhibits glutamate as Ca2+ is needed for fusion of neurotransmitter-carrying vesicles with the plasma membrane
47
Q

what are the 4 types of bipolar cells and what do they do?

A

-rod bipolars: connect up to 50 rods, connect ~4 ganglion cells
-S-cone cells
-Midget bipolars: join one cone with one ganglion cell, foveal
-diffuse bipolars: widespread synaptic connections (up to 7 cones) and many ganglion cells, excitatory or inhibitory, hyperpolarising or depolarising

48
Q

What are horizontal cells?

A

synaptic connections with photoreceptors that hyperpolarize in response to light and release the inhibitory neurotransmitter GABA to provide feedback to cones in gap junctions

49
Q

what are the three different types of horizontal cells and what do they connect to from each side?

A

HI- The dendritic arbour connects with S,M and L cones and the axonal arbour connects with rods
HII- the dendritic arbour connects to S cone and the axonal arbours connect with S, M and L cones
HII -the dendritic arbour connects with L and M cones and the axonal arbour connects with L and M cones

50
Q

give three types of amacrine cells

A

starburst, dopaminergic and A1

51
Q

what do amacrine cells receive from and where do they send messages to?

A

receive from bipolar cells and other amacrine cells and they send messages to bipolar cells, amacrine cells and ganglion cells

52
Q

at least how many types of retinal ganglion cells are there?

A

at least 25 different types

53
Q

where are most of the cell bodies of amacrine cells present?

A

the nuclear cell layer

54
Q

what are the 4 retinal ganglion cells?

A

-parasol
-midget
-blue-yellow
-biplexiform

55
Q

what type are the majority of RGCs and what do they receive from?

A

midget RGCs as they make up 70% of RGCs in the retina and they recieve from midget bipolars

56
Q

what % of RGCs do parasol make up and what do they receive from?

A

8-10% and they receive from diffuse bipolars

57
Q

what are photosensitive RGCs?

A

a small subset of RGCs that express melanopsin and are responsible for photoentrainment and pupillary light reflex

58
Q

what are the characteristics of RGCs axons in the nerve fibre layer of the retina?

A

-connected to the optic disk
-unmyelinated
-eneveloped by extensions of muller cells and astrocytes

59
Q

how is visual prosthesis possible? What does it do?

A

the ordered arrangement of axons and retinal ganglion cells as an electrode can directly stimulate the axons at the end of the optic disk and so can help restore vision in patients with total visual loss due to retinitis pigmentosa as well as AMD

60
Q

what are the three types of cones and their corresponding colours and what are each of their wavelengths they are best responsive to?

A
  • S cones: blue - 437nm
    -M cones: green - 533nm
    -L cones: red - 564nm
61
Q

what colour are red cones most responsive to and how are they different to the other cones?

A

yellow light and unlike others they maintain their responsiveness to light for longer and hence do still respond well to red light

62
Q

for S cones, where is their density lowest, where do they reach max density and what percentage of the total cone population do they make up elsewhere

A

-lowest density in the foveal pit at 3-5%
-reach max density in the foveal slope at 15%
-8%

63
Q

why does perception of blue light reduce as you age?

A

as a result of the macular pigment that covers the fovea as well as the low density of S cones on the fovea.

64
Q

why does the perception of colour change in age?

A

As the crystalline lens yellows

65
Q

How is phototransduction de-activated?

A
  1. deactivation of visual pigment of rhodopsin
  2. deactivation of transducin
  3. deactivation of phosphodiesterase
  4. synthesis cGMP increasing it’s conc again
  5. cGMP-gated channels reopen
  6. cytoplasmic conc. of Ca2+ increases again
  7. translocation of arresting and transducin
  8. recovery of all visual pigments through the retinoid cycle
  9. recovery of the maximal gains of the amplification
66
Q

How is rhodopsin deactivated?

A
  1. GTP-ase activity of activated rhodopsin by rhodopsin kinase
  2. binding of arrestin to disable metarhodopsin II from activating transducins
67
Q

How is phosphodiesterase (PDE) deactivated?
what happens next?

A
  1. GTP-ase transducin alpha bound to gamma PDE converts GTP into GDP
  2. this causes transducin alpha bound GDP to dissociate from PDE and hence deactivating it

cGMP molecules are then synthesised by guanylate cyclase activated by GC activating protein and this then converts GTP nucleotides into cyclic GMP by formation of phosphodiester bonds.

cGMP gated channels are re-opned due to increased affinity for cGMP and increased concentration of cGMP

68
Q

what is the concentration of Ca2+ like during the deactivation of phototransduction?

A

low because this makes it easier for PDE to dissociate from transducin GDP

69
Q

By how much does light intensity change in the environment that our vision functions?

A

in the environment where light intensity changes by over 11 orders of magnitude due how photoreceptors have adapted to ambient light

70
Q

how does adaption of photoreceptors to ambient light affect photosensitivity? Why is this?

A

By causing photosensitivity to decrease which is approximately in inverse proportion to the intensity of the ambient light. This is due to a decreased gain in amplification

71
Q

What are the amplification steps in the phototransduction cascade for light adaptation?

A
  1. light absorption closes cGMP gated channels
  2. internal Ca2+ decreases
  3. cGMP production increases and channel affinity increases
  4. some of the closed channels re-open
  5. photocurrent decreases towards the baseline
72
Q

what is dark adaptation?

A

the recovery of all visual pigments and the maximal sensitivity of photoreceptors in the dark

73
Q

what mechanism is required for dark adaptation?

A

termination of the phototransduction cascade

74
Q

what do opsins do?

A

they activate the phototransduction cascade without chromophore so photoreceptors in the dark behave as if they were exposed to background light

75
Q

what is Stargrdt’s disease caused by and what does it lead to?

A

caused by dysfunction in ABCR protein leading to accumulation of toxic all-trans-retinal causing RPE dysfunction and photoreceptor death

75
Q

what is the interphotoreceptor matrix (IPM) composed of?

A

-enzymes responsible for IPM turnover for example MMPs and TIMPs which are tissue inhibitors of MMPs
-proteoglycans
-glycoproteins
-GAGs
-IRBP (interphotoreceptor retinoid binding protein)

76
Q

what cells is the IPM specific to?

A

rods and cones

77
Q

what are the steps in the retinoid cycle?

A

first of all, vitamin A (all-trans -retinol) is taken up from the blood and this then gets taken up from the interphotoreceptor matric
1. transport by cellular retinoid binding protein
(CRBP)
2. esterification by lecithin retinol acyl transferase (LRAT) with fatty acids
3. human stores of retinyl esters in the RPE are enough to regenerate 2.5 mol eq of rhodopsin
4. isomer hydrolase isomerises and hydrolyses all-trans-retinyl esters to 11-cis-retinol
5. oxidation of 11-cis-retinol to 11-cis-retinal by 11-cis-retinol dehydrogenase
6. transport of 11 cis retinal by cellular retinal binding protein (CRALBP)

78
Q

what is leber’s congenital amaurosis and what is it caused by?

A

rapid loss of vision in childhood or young adulthood due to loss of photoreceptors , caused as a result of the dysfunctional protein RPE65 which leads to the inability of synthesis of 11-cis-retinal

79
Q

how can LCA be treated with gene therapy?

A

by delivering RPE65 with adeno associated virus AAV2 as the vector using an RPE specific promoter to restrict the expression of the RPE transgene only to the RPE cell layer

80
Q

how can LCA be treated pharmacologically?

A

supplementation with 9-cis-retinal to enable synthesis of visual pigments

81
Q

how long does cone and rod pigment to regenerate?

A

-cone pigment takes 10 minutes
-rod pigment takes 20-30 minutes

82
Q

why do cones regenerate visual pigment faster than rods?

A

because muller cells synthesize 11-cis-retinol from all-trans-retinol. only cones can convert 11-cis-retinol to 11-cis-retinal

83
Q

what pigments are responsible for the fovea and its surrounding area to appear yellow?

A

-lutein
-caroteinoid
-xanthophyll
-macular pigment

84
Q

what connects photoreceptor inner segment with outer segment?

A

a modified cilium

85
Q

What happens to the circulating ion current in photoreceptors in response to absorption of light?

A

its value increases and its absolute value decreases

86
Q

what is the plasma membrane potential of photoreceptors in the dark?

A

About -35mV

87
Q

compare the maximum sensitivity for scotopic and photopic vision

A

they are the same

88
Q

what neurotransmitter is released from photoreceptors in the dark?

A

glutamate

89
Q

what happens to bipolar cells in synaptic contact with a hyperpolarized cone?

A

some depolarize while others hyperpolarise

90
Q

what cells in the retina are specialised for setting our circadian clock and pupillary light reflex but not visual perception?

A

ganglion cells expressing an opsin based pigment

91
Q

give 4 reasons for the high concentration of docosahexanoate in the retina

A

-to facilitate changes of conformation of transmembrane receptor proteins
-to allow activation of rhodopsin
-to facilitate regeneration of visual pigment
-to increase fluidity of the disk membrane

92
Q

How is info about the absorption of photons in the retina passed on to the brain via ganglion cell axons?

A

via changes in frequency of generation of action potentials by the ganglion cells

93
Q

what is an approximate concentration of calcium ions in the cytoplasm of rods adapted to saturated light?

A

60nmol/L

94
Q

what is the concentration of calcium in the rod cytoplasm in dark?

A

600nM

95
Q

what is the role of rhodopsin kinase in deactivation of phototransduction?

A

phosphorylation of metarhodopsin II

96
Q

what is the function of muller cells in recovery of the dark-adapted state of photoreceptors?

A

they convert all-trans-retinol to 11-cis-retinol to facilitate generation of visual pigments in cones

97
Q

what is the limiting step in regeneration of high sensitivity of photoreceptors in the healthy human eye in the dark?

A

synthesis of 11-cis-retinal for regeneration of rhodopsin

98
Q

How long does it take the retina to recover the highest sensitivity to light after exposure to bright light bleaching more than 90% of rhodopsin?

A

more than half an hour

99
Q

give 4 events responsible for adaptation of photoreceptors to the dark

A

-influx of calcium to photoreceptor inner segments
-termination of phototransduction cascade
-regeneration of visual pigemnts
-synthesis of 11-cis-retinal

100
Q

what is the role of RPE65 protein in synthesis of 11-cis-retinal

A

it is responsible for the isomeration and hydrolysis of all-trans-retinyl esters

Optometry Class OP4102 (19 decks)

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