Biochemistry of Vision Flashcards

1
Q

The _____ is a small depression in the retina where visual acuity is the highest, it is where the retinal ____ are particularly concentrated

A

Fovea; cones

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2
Q

Function of pigmented epithelial cells

A

Filled with melanin so that residual light is absorbed — doesn’t pass into surrounding cells

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3
Q

Where are pigmented epithelial cells located

A

Outside nerual retina and attached to choroid layer

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4
Q

Axons of ____ cells form the optic nerve

A

Ganglion

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5
Q

What cells allow horizontal processing of light?

A

Horizontal cells

Amacrine cells

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6
Q

The signal transduction pathway of light—>vision originates from a _____ system

Rhodopsin is made up of the receptor ______ and the _______ (retinal) to which it is covalently bound

A

GPCR

Opsin; chromophore

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7
Q

What is the G protein associated with the Rhodopsin GPCR?

A

Transducin

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8
Q

What is the effector protein associated with the rhodopsin GPCR? What does it do?

A

PDE

Cleaves cGMP to GMP (GMP is second messenger)

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9
Q

What surface membrane protein is open in dark conditions, and contributes to partial depolarization in these dark conditions?

A

cGMP-gated channel

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10
Q

What surface membrane component recycles cGMP so that cells go back to depolarized state?

A

Guanylate cyclase

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11
Q

What ancillary protein functions in signal termination by blocking the interaction of rhodopsin with transducin?

A

B-arrestin

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12
Q

What enzyme phosphorylates rhodopsin, providing the first step in signal termination?

A

Rhodopsin kinase

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13
Q

Differentiate rods and cones in terms of sensitivity and spatial resolution

A

Rods = high sensitivity, low spatial resolution

Cones = low sensitivity, high spatial resolution

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14
Q

T/F: there is a high degree of turnover of photoreceptor cells

A

True; it is not a hospitable environment. Exposure to UV radiation, oxygenating species, and glucose

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15
Q

What area of the retina has phagocytosing ability

A

Retinal pigmented epithelium

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16
Q

In the dark, photoreceptor cells are ______and there are _____ neurotransmitters released

A

Depolarized; inhibitory

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17
Q

When the eyes are open, the photoreceptor cells are _________, which removes the _____ neurotransmitters typically released by default

A

Hyperpolarized; inhibitory

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18
Q

What makes rod cells unusual for excitable cells?

A

The membrane is partially depolarized at rest and hyperpolarizes upon stimulation

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19
Q

Partial depolarization of photoreceptor cells at rest means the NT _____ is continuously released.

_____ and _____ are the most common inhibitory neurotransmitters and as such inhibit the optic nerve bipolar cells

A

Glutamate

GABA; glycine

[note that glutamate is normally excitatory but in this case is inhibitory]

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20
Q

Hyperpolarization of photoreceptor cells stops ____ transmission and relieves the inhibition of the optic nerve bipolar cells

A

Glutamate

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21
Q

Rhodopsin is homologous to what type of receptor?

A

Beta-adrenergic receptor

[nerve cells in which epinephrine/NE acts as NT]

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22
Q

The retinal portion of rhodopsin is derived from _______

A

Vitamin A

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23
Q

The aldehyde of retinal forms a schiff base with the amine of ______, which when photoactivated becomes protonated

A

Lysine

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24
Q

Rhodopsin goes through several intermediate conformations of various names but the activated version is known as ________

A

Metarhodopsin II

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25
Q

cGMP PDE catalyzes what reaction with cGMP?

What effect does this have on the photoreceptor cell?

A

Hydrolysis of cGMP to 5’GMP

Lower concentration of cGMP causes hyperpolarization of visual cells —> visual signal transduction

26
Q

Describe activation of transducin G protein

A

Light activates Gt —> which activates cGMP PDE —> catalyzes hydrolysis of cGMP to 5’GMP

27
Q

Activation of rod photoreceptor:

Photon of light interacts with _____ in a photoreceptor cell, which then isomerizes to the all-trans configuration. This activates a _____ by conformational change in disk membrane.

A

Retinal; rhodopsin

28
Q

Activated rhodopsin makes repeated contacts with _____ molecules, catalyzing its activation by release of GDP in exchange for cytoplasmic GTP

A

Transducin

[activated G protein binds inhibitory gamma subunits of PDE, activating its alpha and beta subunits]

29
Q

Once PDE is activated, it hydrolyzes cGMP and the ____channels close which causes hyperpolarization due to ongoing efflux of ____ ions which cause voltage gated Ca channels to close

A

Sodium; potassium

30
Q

Once hyperpolarization occurs, ______ _____ synthesizes cGMP, the second messenger in the cascade

A

Guanylyl cyclase

31
Q

As the calcium level in the photoreceptor cell drops, the amount of _____ that is released also drops. This decrease causes ____ of the cell

A

Glutamate; depolarization

32
Q

Role of calcium in dark conditions

A

In dark conditions, Ca and Na enter the rod OS through cGMP-gated ion channels

Calcium influx balances efflux through channel exchanger

33
Q

Role of Ca in light conditions

A

Ca influx through cGMP channel stops but exchanger export continues (net loss of Ca)

This drop in intracellular Ca stimulates the activity of guanylate cyclase, restoring the [cGMP] and re-opens cGMP-gated ion channels

34
Q

Signal termination begins with blockage of transducin. How is light-activated rhodopsin blocked from activating transducin?

A

Rhodopsin kinase phosphorylates COOH terminus of metarhodopsin II at Thr and Ser, allowing binding by arrestin and preventing interaction with transducin

35
Q

The first step in signal termination is light-activated rhodopsin blockage from activating transducin. Next, there is rapid hydrolysis of ATP to ADP, causing dissociation of tranducin from _____ and reassociation of the beta and gamma subunits. Finally, elevated _____ levels re-open cGMP-gated ion channels (inhibitory) and ________ ______ synthesized cGMP from GTP

A

PDE; cGMP; guanylate cyclase

36
Q

In light, low cGMP levels close ____ and ____ channels, reducing intacellular concentration of these ions.

During recovery, the low _____ levels induce recovery

A

Na; Ca

Ca

37
Q

By controlling the rate of cGMP synthesis, ____ levels govern the rate by which the system is restored

A

Calcium

38
Q

The purpose of the retinoid cycle is to regenerate what?

A

11-cis-retinal

39
Q

While not a part of the neural retina, what layer is essential for normal function and survival of photoreceptors, existing in close proximity to the outer segments?

A

RPE cells

40
Q

Principle enzymes for 11-cis-retinal regeneration in the visual cycle

What happens when this enzyme is dysfunctional?

A

RPE 65 (LRAT also important)

RPE 65 Dysfunction —> retinitis pigmentosa (loss of vision, pigment depositions, loss of periphery)

41
Q

Events of retinoid cycle in the rod cell

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

Exportation of all-trans-retinol (with help of iRBP)

42
Q

Events of retinoid cycle in retinal pigmented epithelium

A

All-trans-retinol uptake into RPE and translocation to ER

Esterification to all-trans-retinyl ester by LRAT

Conversion to 11-cis retinol

Oxidation from 11-cis retinol to 11-cis retinal

Exportation of 11-cis retinal

43
Q

Once 11-cis retinal is regenerated in RPE and exported back to rod cell, it undergoes covalent attachment to ______ forming a functional _____

A

Opsin; rhodopsin

44
Q

Cone receptors are homologues of _____

A

Rhodopsin

45
Q

T/F: photoreceptor proteins are highly conserved evolutionarily

A

True

46
Q

Rearrangements during DNA replication may lead to what complication of vision?

A

Loss of visual pigment genes — color blindness

47
Q

Color blindness heritability

A

X-linked recessive

48
Q

_____ is produced in the retina from vitamin A, from dietary beta carotene

_____ and _____ are used to maintain epithelial cells

A

Retinal

Retinol; retinoic acid

[retinol has hydroxyl group, retinoic acid has carboxyl group, retinal has aldehyde]

49
Q

Consequences of vitamin A deficiency

A

Night blindness
Xeropthalmia
Keratinization of epithelium (GI, resp)
Dry, scaly skin

50
Q

Vitamin A deficiency is the most important nutritional disorder with respect to the ______, characterized by Bitot spots, xerosis, and keratomalacia

A

Cornea

51
Q

What are bitot spots

A

Build-uup of keratin superficially in conjunctiva. Usually oval, rectangular, or irregular in shape, “foamy” in appearance

52
Q

Abnormal dryness of the conjunctiva and cornea of the eye, with inflammation and ridge formation

A

Xeropthalmia

Classifications:
Night blindness
Conjunctival xerosis
Bitot spots
Corneal xerosis
Corneal ulceration/keratomalacia
Corneal scar
Xerophthalmic fundus
53
Q

Non-visual presentations of Vit A deficiency

A
Growth impediment
Poor wound healing
Dry skin
Follicular hpyerkeratosis
Alopecia
Bronchitis
Pneumonia
54
Q

Complications of excess vitamin A

A

Liver toxicity

Joint pain

55
Q

Infants exposed to _____ in the womb may have birth defects like cleft palate and heart abnormalities

A

Isotretinoin

56
Q

Nyctalopia

A

Night blindness; disorder of rod cells

Most often associated with vitamin A deficiency leading to insufficient rhodopsin

57
Q

Xerosis

A

Metaplasia of conjunctival epithelium to stratified squamous type with keratinized surface

58
Q

T/F: vitamin A plays an unknown role in maintaining specialized ocular epithelia; specifically loss of goblet cells

A

True

59
Q

Macular degeneration is degeneration of what 2 components?

What are the effects?

A

RPE and retina

Results in loss of central field vision, poor night vision

complications: atrophy, macular hemorrhage, pigmentation, macular edema, subretinal fluid

60
Q

_____ _____ like lutein and zeaxanthin play a direct role in the protection of the retina against damage with things like macular degeneration

A

Macular carotenoids (xanthophylls)

61
Q

Mutations in what transporter are implicated in macular degeneration?

A

ABC4 (an ABC transporter that works in clearance of all trans retinal derivatives from photoreceptors)

62
Q

Which two opsin proteins are x-linked?

A

Red

Green