Biochemistry Of The Visual System

Question 1

Describe rods

Answer 1

Vision in low light levels
Contain rhodopsin (cannot detect color)
High sensitivity and low spatial resolution

Question 2

Describe cones

Answer 2

Color detection
Three opsins (red, green and blue)
Low sensitivity and high spatial resolution

Question 3

What is the convergence of rods?

Answer 3

Rods can respond to a single photon
Many rods converge into a single bipolar cell
Many of these bipolar cells contact a single amacrine cell
This allows for highest levels of sensitivity but sacrifices resolution

Question 4

What is the convergence of cones?

Answer 4

Cones need ~100 photons to respond
One cone directly contacts only one bipolar cell
This arrangement allows for best resolution but sacrifices sensitivity

Question 5

When a photoreceptor is stimulated by photons/light what happens in the cell?

Answer 5

The cell becomes hyperpolarized and they release less NT (glutamate)

Question 6

In conditions of darkness the photoreceptor cells are what?

Answer 6

Consistently depolarized and constantly release glutamate

Question 7

Which proteins and receptors located on the disc membranes of the outer segments are involved with signal transduction?

Answer 7

Signal transduction pathway originates from a GPCR system
Opsin (7TM receptor)
Transducin (G protein)
cGMP phosphodiesterase which acts as an effector protein and cleaves cGMP to GMP
Peripherin (structural protein)

Question 8

What receptors are on the surface membrane of the outer segment?

Answer 8

cGMP gated Na channel (Ca leak channel) which is open in dark conditions and contributes to depolarization (closed in light conditions) 
Na/Ca exchanger (Ca continues out after illumination) 
Guanylate cyclase (GTP -> cGMP + PPi) which recycles cGMP

Question 9

Which proteins are involved with desensitization of signal transduction?

Answer 9

Beta-arrestin which performs signal termination by blocking the intersection of rhodopsin with transducin
Rhodopsin kinase which performs the first step in signal termination (phosphorylation)

Question 10

Describe the structure of rhodopsin

Answer 10

Homologous to beta-adrenergic receptor
Lysine-296 is covalently bound to 11-retinal and is located in the center of the 7TM
Retinal is derived from vitamin A and is a chromophore
Aldehyde of retinal forms a Schiff base with the amine of lysine

Question 11

What are the absorption wavelengths for the different forms of retinal?

Answer 11

Free retinal = 370nm
Unprotonated Schiff base retinal = 380nm
Protonated Schiff base retinal = >440nm
Thus photoactivated lysine is protonated

Question 12

Describe photon induced isomerization

Answer 12

Energy of the photon causes geometric isomerization which translates to atomic motion
This conformational change upon light induction mimics the conformational change that occurs upon ligand binding in other 7TMs
11-cis retinal -> 11-trans retinal
Causes 5A conformational shift of Schiff base nitrogen

Question 13

What is the activated form of rhodopsin known as?

Answer 13

Metarhodopsin II (Rh*)

Question 14

Describe photoreceptor opsins

Answer 14

Cone receptor opsins are homologous of rod receptor opsins
3 varieties
Blue (absorbs at 420-460nm), green (530nm) and red (>560nm)

Question 15

Which chromosomes code for each photoreceptor opsin?

Answer 15

Rhodopsin chromosome 3
Blue opsin chromosome 7
Red and green are on the X chromosome

Question 16

Explain the genetic expression of red/green colorblindness

Answer 16

Expression of the red/green opsins affected in red/green color blind affected individuals is inherited maternally
Assigned male at brith affected with red/green color blindness wont pass this trait on to offspring
Unaffected assigned female at brith carriers can pass R/G color blindness onto their AMAB offspring

Question 17

What are the three ways signal transduction can be terminated (desensitized)?

Answer 17

1. Light activated rhodopsin blocked from activating transducin
2. Rapid hydrolysis of GTP to GDP causes dissociation of alpha subunit from PDE and re-association with beta and gamma subunits (innate GTPase activity of transducin)
3. Elevated cGMP levels re-open cGMP gated Na channels (ganylate cyclase synthesizes cGMP from GTP)

Question 18

Describe how light activated rhodopsin can be blocked from activating transducin

Answer 18

Rhodopsin kinase phosphorylates the C terminus of metarhodopsin II (Rh*) at Thr and Ser allowing binding by arrestin
Binding of arrestin prevents the interaction between rhodopsin and transducin

Question 19

What is the role of Ca in termination of the phototransduction cascade?

Answer 19

In light conditions low cGMP levels close Na and Ca channels reducing their intracellular concentrations
During activation, PDE activity decreases intracellular cGMP by promoting its cleavage —>
cGMP gated Na channels close —> hyperpolarization —> closed Na/Ca channels lead to a decrease in intracellular Ca levels which results in recovery -> guanylate cyclase activity increases -> intracellular cGMP levels increase -> Na/Ca channels open causing depolarization of the cell

Question 20

What are the three different structures of vitamin A?

Answer 20

Based on functional groups

Hydroxyl (retinol), carboxyl (retinoic acid) and aldehyde (retinal)

Question 21

What is the function of retinol and retinoic acid?

Answer 21

Used to maintain epithelial cells
Important for maintenance of cornea and conjunctiva
Also helps maintain epithelial tissues in skin, intestines, lungs, bladder and inner ear
Supports T cell function, male and female reproduction and fetal development

Question 22

What is xeropthalmia?

Answer 22

Abnormal dryness of the conjunctiva and cornea of the eye typically associated with vitamin A deficiency
Second most prevalent nutritional disorder
With a decrease in vitamin A levels the cornea can undergo complete necrosis

Question 23

Vitamin A deficiency results in what?

Answer 23

Changes in mucosal surfaces throughout the body
Resulting in keratinizing metaplasia in the lining of epithelia of the lungs and intestines which is responsible for the respiratory and GI sx of severely depleted children

Question 24

What are the dietary sources of vitamin A?

Answer 24

Carrots, leafy greens, sweet potatoes, squash, broccoli and animal products (eggs, dairy, fish and liver)

Question 25

Describe disorders associated with vitamin A deficiency

Answer 25

Malnutrition due to inadequate intake or absorption causes deficiencies in vitamin A that manifest as night blindness, visual impairment, xeropthalmia (dry eye syndrome) and Bitot’s spots (due to keratin debris in the conjunctiva)
Additional presentations of deficiency include growth impediment, failure of wounds to heal well, dry skin, follicular hyperkeratosis, alopecia and lung conditions
Excess vitamin A due to copious intake of supplements causes liver toxicity and joint pain
Infants exposed to isotretinoin (accutane) in the womb may have brith defects such as cleft palates and heart abnormalities

Question 26

What is golden rice?

Answer 26

First genetically designed bio-fortified food
Fortified with beta carotene
Provided >80% of daily caloric intake in over half of the worlds population

Question 27

What is the principal site of 11-cis retinal regeneration in the retinoid cycle?

Answer 27

The RPE

Question 28

What is retinitis pigmentosa?

Answer 28

Due to dysfunction of LRAT and RPE65
Decreased night vision and peripheral vision
Progressive loss of rods and eventual loss of cones
Bony spicule formation in the RPE also occurs

Question 29

What is macular degeneration?

Answer 29

Degeneration of the macula in the retina which results in the loss of central field of vision
ABC transporters work in clearance of all-trans retinal from photoreceptors and mutations in ABCA4 are known to cause this disease
Males and females equally affected
Peak incidence 75-80 years old

Question 30

What are the risk factors for macular degeneration?

Answer 30

Advancing age (especially over 70), hx of smoking within past 20 years, dietary factors (low intake of antioxidants, Zn and omega-3 FAs; high fat intake), obesity and being Caucasian