Biochemistry of the Visual System

Question 1

Photoreceptors in the dark vs light

Answer 1

• In dark: cGMP-gated Na+ channel (Ca2+ leak channel) open and cell is depolarized –> constantly release glutamate onto bipolar cells to inhibit them
• In light: Na+ channels closed and cell is hyperpolarized due to rapid hydrolysis of cGMP via phosphodiesterase –> less release of glutamate onto bipolar cells

Question 2

Absorption wavelength of: free retinal

Answer 2

370 nm

Question 3

Absorption wavelength of: unprotonated Schiff base retinal

Answer 3

380 nm

Question 4

Absorption wavelength and chromosome location of: protonated Schiff base (rhodopsin)

Answer 4

• 440-500 nm

* Chromosome 3

Question 5

Where is the 11-retinal bound to in the rhodopsin receptor?

Answer 5

Covalently bound to Lysine-296 w/in center of the receptor to form a Schiff base

Question 6

Absorption wavelength and chromosome location of: blue opsin

Answer 6

• 420 nm

* Chromosome 7

Question 7

Absorption wavelength and chromosome location of: red opsin

Answer 7

• > 560 nm

* X chromosome

Question 8

Absorption wavelength and chromosome location of: green opsin

Answer 8

• 530 nm

* X chromosome

Question 9

Red/blue color blindness hereditary pattern

Answer 9

• X-linked recessive
• Carrier mother + unaffected father –> 1 unaffected son, 1 unaffected daughter, 1 carrier daughter, 1 affected son
• Affected father + unaffected mother –> 2 unaffected sons, 2 carrier daughters

Question 10

Methods of signal transduction termination

Answer 10

1. Light-activated rhodopsin blocked from activating transducin (Rhodopsin kinase phosphorylates C-terminus of metarhodopsin II at Threonine and Serine –> Beta-arrestin binds to it and prevents interaction w/ transducin)
2. Rapid hydrolysis of GTP to GDP due to innate GTPase activity of transducin –> dissociation of alpha-subunit from PDE
3. Increased Gyanylate cyclase activity during recovery –> elevated cGMP lvls re-open cGMP-gated Na+ channels

Question 11

Name how the 3 vitamin A structures differ

Answer 11

• Based on functional groups:
  a. Retinol - hydroxyl (-OH)
  b. Retinoic acid - carboxyl (-CO,OH)
  c. Retinal - aldehyde (-CO,H)

Question 12

Xeropthalmia

Answer 12

• Abnormal dryness of conjunctiva and cornea of eye

- Typically associated w/ vitamin A deficiency

Question 13

Clinical of vitamin A deficiency

Answer 13

• Malnutrition due to inadequate intake or absorption –> deficiencies manifesting as:
  a. Night blindness
  b. Visual impairment
  c. Xeropthalmia (dry eye syndrome)
  d. Bitot’s spots (due to keratin debris in conjunctiva)

Question 14

Symptoms of vitamin A deficiency

Answer 14

a. Growth impediment
b. Failure of wounds to heal well
c. Dry skin
d. Follicular hyperkeratosis
e. Alopecia
f. Lung conditions (e.g. bronchitis and pneumonia)

Question 15

Excessive vitamin A can cause

Answer 15

• liver toxicity

- joint pain

Question 16

How does isotretinoin (Accutane) impact infants in womb?

Answer 16

May result in birth defects such as cleft palates and heart abnormalities

Question 17

Retinitis pigmentosa

Answer 17

• Oxidative and inflammatory changes in the retinal pigmented epithelium and retina due accumulation of retinoid metabolites
• Decreased night vision (caused by decrease in rod cells) and peripheral vision (caused by bony spicule formation)
• Progressive loss of rod cells and eventual loss of cone cells
• Due to lecithin retinol acyl transferase (LRAT), RPE65 dysfunction
• Bony spicule formation in the retinal pigmented epithelium

Question 18

Macular degeneration

Answer 18

• Degeneration of the macula resulting in central field vision loss
• Mutations in ABC4 implicated but other risk factors include: >70 yo, smoking, dietary factors, obesity, caucasian