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COM: Neuro (Exam I) > Lecture 9: Biochemistry Of Vision > Flashcards

Lecture 9: Biochemistry Of Vision Flashcards

1
Q

What are the 3 major cell types of the retina?

A

Photoreceptors
Interneurons (bipolar, horizontal cells, amacrine cells)
Ganglion cells

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2
Q

What is the order of circuitry of light through the 3 cell types in the retina?

A

Photoreceptors -> interneurons -> ganglion cells

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3
Q

Rods are slender, elongated structures that each contains a stack of disks. Each disk is a membrane-enclosed sac densely packed with photoreceptor molecules. The photoreceptor molecule in rods is ____________.

A

Rhodopsin -> cant detect color!

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4
Q

Between rods and cones, which has high sensitivity and low spatial resolution, and which has a low sensitivity and high spatial resolution?

A

Rods have high sensitivity and low spatial resolution

Cones have low sensitivity and high spatial resolution

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5
Q

What is the photoreceptor molecule in cones?

A

Three opsins (red, green, blue)

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6
Q

What does rhodopsin (photoreceptor molecule found in rods) consist of?

A

Opsin (protein) + 11 cis-retinal (derived from vitamin A)

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7
Q

How is rhodopsin formed chemically?

A

Lysine-296 in opsin covalently binds to 11-cis retinal causing aldehyde of retinal to form a schiff base with amine of lysine. The schiff base then becomes protonated and you have your rhodopsin product

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8
Q

What receptor is rhodopsin structurally similar to?

A

Beta2-adrenergic receptor

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9
Q

At what wavelength is rhodopsin maximally absorbed?

A

500nm

  • Normal range of light is 450-700
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10
Q

How does light affect the isomerization of rhodopsin?

A

Rhodopsin is found in the 11-cis-retinal form and converts to the 11-trans-retinal form when light hits it

Also causes a 5A conformational shift in schiff-base nitrogen (moves lys)

**Now called metarhodopsin II

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11
Q

What is the G protein associated with rhodopsin?

A

Transducin

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12
Q

Explain signal termination of rhodopsin

A

Rhodopsin kinase phosphorylates rhodopsin at Thr and Ser allowing binding by arresting and preventing interaction with Transducin

Transducin has intrinsic GTPase activity. Hydrolysis of GTP -> GDP causes dissociation of Transducin from PDE and reassociation with beta/gamma subunits

Guanylate cycase synthesizes cGMP from GTP

Elevated cGMP levels re-open cGMP-gated ion channels

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13
Q

How does Ca2+ control activity of guanylate cyclase associated with the rhodopsin GPCR?

A

Ca2+ inhibits activity of guanylate cyclase.

In dark -> Ca and Na enter rod through cGMP-gated ion channels but influx is balanced by efflux through a Na/K/Ca exchanger

In light -> Ca influx thorugh cGMP channel stops but exchanger continues which reduces IC Ca, stimulating activity of guanylate cyclase, restoring the cGMP concentration and re-opening the cGMP-gated ion channels

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14
Q

Rods and cones release _____________ (NT) in dark when depolarized. Light causes ________________ (depolarization/hyperpolarization), which reduces this neurotransmitter release

A

Glutamate; hyperpolarization

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15
Q

When rods and cones are signaling to the brain, glutamate binds to receptors on ___________ cells which become depolarized/or hyperpolarized. These cells connect to _____________ cells, which depolarize in turn creating AP thats transmitted to the brain via the _____________ nerve

A

Bipolar cells; ganglion cells; optic nerve

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16
Q

The retina has lateral cell connections via horizontal and amacrine cells which secrete ______________, an inhibitory NT, which helps modulate vision

A

GABA

17
Q

What 2 opsins of cones are almost identical?

A

Red and green, therefore red-green colorblindness is most common

18
Q

What is the goal of the retinoid cycle?

A

Regeneration of 11-cis-retinal

**Defects in this pathway causes visual impairment or blindness in humans

19
Q

What happens in the rod cell during the retinoid cycle?

A

Light-induced change from 11-cis to all-trans -> release of all-trans-retinal from opsin -> enzymatic reduction of all-trans-retinal to all-trans-retinol -> export of all-trans-retinol

20
Q

What happens in the retinal pigmented epithelium (RPE) during the retinoid cycle?

A

Uptake of all-trans-retinol -> translocation to ER -> esterification to all-trans-retinyl ester by LRAT -> conversation to 11-cis-retinol by RPE65 -> enzymatic oxidation from 11-cis-retinol to 11-cis-retinal by RDH -> export of 11-cis-retinal

21
Q

In mammals, 10% of rods are shed each day. When does peak rod shedding occur? How about cone shedding?

A

Peak rod shedding = in the morning

Peak cone shedding = after dark

22
Q

Retinitis pigmentosa is a group of inherited retinopathies. What mutations cause this?

A

Mutations in rhodopsin and other photoreceptor proteins (peripherin, PDE) which affects disk morphology, photoreceptor structure and function and renewal

23
Q

What is retinitis pigmentosa characterized by?

A

Loss of night vision followed by peripheral vision. Leads to degeneration causing complete blindness

24
Q

What are some vision disorders caused by vitamin A deficiency?

A

Night blindness
Xerophthalmia (dry eye syndrome)
Bitot’s spots (due to keratin debris in the conjunctiva)
Visual impairment

25
Q

Why is vitamin A important for vision?

A

Its the precursor for retinal

26
Q

Age-related Macular degeneration is the leading cause of vision impairment/blindness in the elderly. What region of the eye does this effect and what pathological processes play a key role?

A

Effects the macular region of the retina; pathological processes in lipid metabolism, oxidative stress and inflammation play a key role

27
Q

What are risk factors for age-related macular degeneration?

A

Age
Smoking
Genetic predisposition

28
Q

What are the 2 forms of age-related macular degeneration?

A

Dry form = accumulation of lipid rich extracellular deposits, degeneration of RPE, and secondary photoreceptor loss

Wet form = choroidal neovascularization -> less common, results in severe vision loss

29
Q

Mutation in ABC transporters is linked to what vision diseases?

A

Stargardt’s disease (autosomal recessive form of juvenile macular degeneration)

Cone-rod dystrophy

Retinitis pigmentosa

Age-related macular degeneration

30
Q

How do mutation in ABC transporters cause vision disease?

A

Cell death due to accumulation of toxic by-products of visual cycle

Also accumulation of all trans-retinal

**Accumulation of these 2 produces cellular debris, which in turn generate oxidative stress

31
Q

Lutein and Zeaxanthin are both examples of what?

A

Macular carotenoids

32
Q

What is the function of macular carotenoids?

A

Protect ocular tissue including retina against photo-oxidative damage -> act as filters for damaging blue light and serve as antioxidants quenching excited triplet state molecules or singlet molecular oxygen and scavenge further ROS

COM: Neuro (Exam I) (13 decks)

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