Biochemistry of Vision

Question 1

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

Answer 1

Fovea; cones

Question 2

Function of pigmented epithelial cells

Answer 2

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

Question 3

Where are pigmented epithelial cells located

Answer 3

Outside nerual retina and attached to choroid layer

Question 4

Axons of ____ cells form the optic nerve

Answer 4

Ganglion

Question 5

What cells allow horizontal processing of light?

Answer 5

Horizontal cells

Amacrine cells

Question 6

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

Answer 6

GPCR

Opsin; chromophore

Question 7

What is the G protein associated with the Rhodopsin GPCR?

Answer 7

Transducin

Question 8

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

Answer 8

PDE

Cleaves cGMP to GMP (GMP is second messenger)

Question 9

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

Answer 9

cGMP-gated channel

Question 10

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

Answer 10

Guanylate cyclase

Question 11

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

Answer 11

B-arrestin

Question 12

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

Answer 12

Rhodopsin kinase

Question 13

Differentiate rods and cones in terms of sensitivity and spatial resolution

Answer 13

Rods = high sensitivity, low spatial resolution

Cones = low sensitivity, high spatial resolution

Question 14

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

Answer 14

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

Question 15

What area of the retina has phagocytosing ability

Answer 15

Retinal pigmented epithelium

Question 16

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

Answer 16

Depolarized; inhibitory

Question 17

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

Answer 17

Hyperpolarized; inhibitory

Question 18

What makes rod cells unusual for excitable cells?

Answer 18

The membrane is partially depolarized at rest and hyperpolarizes upon stimulation

Question 19

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

Answer 19

Glutamate

GABA; glycine

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

Question 20

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

Answer 20

Glutamate

Question 21

Rhodopsin is homologous to what type of receptor?

Answer 21

Beta-adrenergic receptor

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

Question 22

The retinal portion of rhodopsin is derived from _______

Answer 22

Vitamin A

Question 23

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

Answer 23

Lysine

Question 24

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

Answer 24

Metarhodopsin II

Question 25

cGMP PDE catalyzes what reaction with cGMP? What effect does this have on the photoreceptor cell?

Answer 25

Hydrolysis of cGMP to 5’GMP Lower concentration of cGMP causes hyperpolarization of visual cells —> visual signal transduction

Question 26

Describe activation of transducin G protein

Answer 26

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

Question 27

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.

Answer 27

Retinal; rhodopsin

Question 28

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

Answer 28

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

Question 29

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

Answer 29

Sodium; potassium

Question 30

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

Answer 30

Guanylyl cyclase

Question 31

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

Answer 31

Glutamate; depolarization

Question 32

Role of calcium in dark conditions

Answer 32

In dark conditions, Ca and Na enter the rod OS through cGMP-gated ion channels Calcium influx balances efflux through channel exchanger

Question 33

Role of Ca in light conditions

Answer 33

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

Question 34

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

Answer 34

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

Question 35

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

Answer 35

PDE; cGMP; guanylate cyclase

Question 36

In light, low cGMP levels close ____ and ____ channels, reducing intacellular concentration of these ions. During recovery, the low _____ levels induce recovery

Answer 36

Na; Ca Ca

Question 37

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

Answer 37

Calcium

Question 38

The purpose of the retinoid cycle is to regenerate what?

Answer 38

11-cis-retinal

Question 39

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?

Answer 39

RPE cells

Question 40

Principle enzymes for 11-cis-retinal regeneration in the visual cycle What happens when this enzyme is dysfunctional?

Answer 40

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

Question 41

Events of retinoid cycle in the rod cell

Answer 41

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)

Question 42

Events of retinoid cycle in retinal pigmented epithelium

Answer 42

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

Question 43

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

Answer 43

Opsin; rhodopsin

Question 44

Cone receptors are homologues of _____

Answer 44

Rhodopsin

Question 45

T/F: photoreceptor proteins are highly conserved evolutionarily

Answer 45

True

Question 46

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

Answer 46

Loss of visual pigment genes — color blindness

Question 47

Color blindness heritability

Answer 47

X-linked recessive

Question 48

_____ is produced in the retina from vitamin A, from dietary beta carotene _____ and _____ are used to maintain epithelial cells

Answer 48

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

Question 49

Consequences of vitamin A deficiency

Answer 49

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

Question 50

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

Answer 50

Cornea

Question 51

What are bitot spots

Answer 51

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

Question 52

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

Answer 52

Xeropthalmia ``` Classifications: Night blindness Conjunctival xerosis Bitot spots Corneal xerosis Corneal ulceration/keratomalacia Corneal scar Xerophthalmic fundus ```

Question 53

Non-visual presentations of Vit A deficiency

Answer 53

``` Growth impediment Poor wound healing Dry skin Follicular hpyerkeratosis Alopecia Bronchitis Pneumonia ```

Question 54

Complications of excess vitamin A

Answer 54

Liver toxicity | Joint pain

Question 55

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

Answer 55

Isotretinoin

Question 56

Nyctalopia

Answer 56

Night blindness; disorder of rod cells Most often associated with vitamin A deficiency leading to insufficient rhodopsin

Question 57

Xerosis

Answer 57

Metaplasia of conjunctival epithelium to stratified squamous type with keratinized surface

Question 58

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

Answer 58

True

Question 59

Macular degeneration is degeneration of what 2 components? What are the effects?

Answer 59

RPE and retina Results in loss of central field vision, poor night vision complications: atrophy, macular hemorrhage, pigmentation, macular edema, subretinal fluid

Question 60

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

Answer 60

Macular carotenoids (xanthophylls)

Question 61

Mutations in what transporter are implicated in macular degeneration?

Answer 61

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

Question 62

Which two opsin proteins are x-linked?

Answer 62

Red | Green