Retinal Metabolism - Week 5 Flashcards

1
Q

For what processes in the body is ATP usage the highest?

A
  • Dark current
  • Neurotransmission
  • Ionic Transport
  • cGMP, GTP production
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2
Q

What is the metabolic role of NADPH (a reductin)?

A

is used in:

  • chromophore recycling
  • membrane synthesis
  • as an antioxidant
  • membrane integrity + photopigment function
  • RNA synthesis/DNA repair
  • Vasomotor regulation
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3
Q

What is the metabolic role of Ribose-5-Phosphate?

A

is used in RNA synthesis

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4
Q

Where in the rod photoreceptor does Rhodopsin de-activation occur?

A

Outer segment

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5
Q

Where in the rod photoreceptor is rhodopsin found?

A

Outer segment

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6
Q

Where in the photoreceptor does cGMP synthesis occur?

A

Outer segment

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7
Q

What is the main role of the photoreceptor inner segment?

A

Provide ATP for the sodium potassium pump

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8
Q

What is the main role of the photoreceptor outer segment?

A

Absorption of light

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9
Q

Where in the photoreceptor does phototransduction occur?

A

Outer segment

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10
Q

Briefly describe the outer segment of a photoreceptor

A

are actually modified cilia that contain discs filled with opsin (the molecule that absorbs photons), and has voltage gated sodium channels

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11
Q

Where in the photoreceptor does RNA synthesis take place?

A

Inner segment

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12
Q

What results from impaired transport or defective proteins in the inner segment of the photoreceptor?

A

Some form of retinal degeneration e.g. RP

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13
Q

What pathway is the primary source of NADPH?

A

Pentose Phosphate Pathway

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14
Q

Where does glucose get stored?

A

In the muscle

Note: it does NOT get stored in the brain or retina

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15
Q

What is the main product of Glycolysis?

A

Precursors that feed kreb cycle (and a little bit of ATP as well)

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16
Q

Briefly describe the Kreb/TCA cycle

A

a series of enzymatic reactions that loop back on themselves where you are breaking carbon off molecules resulting in the carbons getting shorter as you go around the cycle

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17
Q

What happens when you break a carbon off a molecule in the Kreb/TCA cycle?

A

you generate a reductin (either NADH or FADH)

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18
Q

How do reductins help generate ATP?

A

When added to the ETC, reductins can drive an electron gradient to create ATP

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19
Q

What happens to the amino acids produced by the Kreb/TCA cycle?

A

They become our Neurotransmitters

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20
Q

What 2 things provide vascular supply to the two halves of the iris?

A

Minor arterial circle - bottom half

Aqueous - top half

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21
Q

Where does the ophthalmic artery originate from?

A

Internal carotid artery

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22
Q

Where do the the short posterior ciliary arteries enter the eye?

A

They pierce the sclera posteriorly to enter the choroid layer

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23
Q

Where do the long posterior ciliary arteries enter the eye?

A

travel medially and laterally along the sides of the optic nerve and past the anterior aspect of the eyeball, piercing the choroid layer

24
Q

Which part of the retina does the central retinal artery supply?

A

internal surface of the retina (it pierces close to the optic nerve)

25
Q

What supplies the outer layer of the retina?

A

Choroidal vessels (choriocapilaris)

26
Q

What supplies the inner layer of the retina?

A

Retinal vessels and their capillaries

27
Q

Where in the posterior segment of the eye is oxygen tension maximal?

A

Choriocapillaris

28
Q

Compare the autoregulation of the blood supply to the outer and inner retina. Where does it occur?

A

Inner layers of retina = locally autoregulated (via myogenic + metabolic mechanisms)

Outer layers of retina = NO local autoregulation

29
Q

Compare the flow rate for the outer and inner retina. Where is it highest?

A

Outer retina = Very high flow rate

Inner retina = Low flow rate

30
Q

Compare the venous oxygen saturation for the outer and inner retina? Where is it highest?

A

Outer retina = High venous oxygen saturation

Inner retina = Low venous oxygen saturation

31
Q

Define autoregulation

A

Intrinsic ability to maintain a constant blood flow despite changes in perfusion pressure

32
Q

How does autoregulation compensate for low blood pressure?

A

low b.p – reduced sheer – increased NO (vasodilator) – relaxes muscle fibres – increased vessel diameter

*Note: increasing vessel diameter allows us to get more blood to the area (increased blood flow)

33
Q

How does autoregulation compensate for high blood pressure?

A

high b.p – increased sheer – increased Endothelin-1 release from vessel wall – reduced vessel diameter

Endothelin-1 is a vasoconstrictor

*Note: since we have high b.p, we constrict the vessel supplying the area so less blood flows to it.

34
Q

Define sheer stress

A

The dragging force of the blood on the vessel wall

35
Q

When is oxygen tension lower, in the dark or light?

A

Oxygen tension is lower in the dark. O2 is being consumed in dark current

36
Q

How much O2 is generally utilised by the retina per hour?

A

1.5umol/mg dry weight/hour

37
Q

Which uses more oxygen: retina or brain?

A

Retina (2x more than brain)

38
Q

Where is oxygen used in the retina?

A

70% of O2: TCA cycle, glycolysis, oxidative phosphorylation

Remainder of O2: oxidation of pyruvate, lactate, amino acids

39
Q

What mechanism actively transports glucose across membranes?

A

Na+/Glucose symports

40
Q

What mechanisms passively transport glucose across membranes?

A

Glucose transporter (GLUT) family. 5 types: GLUT1-5. GLUT-1 most important.

are ‘uniports’

41
Q

What are the normal glucose levels in serum?

A

4-8mM

42
Q

is ATP excitatory or inhibitory for GLUT-1

A

inhibitory

43
Q

at what serum glucose level does GLUT-1 operate at 50% efficiency?

A

1mM

44
Q

Where is GLUT-1 found

A

Basically everywhere in the retina. Anything that’s brown

45
Q

Where is GLUT3 found?

A

Inner retina

46
Q

Where is GLUT-2 found?

A

Only found in ELM and ILM (External and Internal limiting membrane)

*it’s a muller cell glucose transporter

47
Q

What what serum glucose levels does GLUT-2 operate at 50% efficiency?

A

15mM

48
Q

Where is GLUT-4 and GLUT-5 found?

A

Nowhere in the retina

49
Q

What can you use as an indicator of the level of oxygen usage in an area of the retina?

A

The level of certain aerobic vs anaerobic enzymes
Aerobic: Malate dehydrogenase (MDH) and Glutamate dehydrogenase (GDH)

Anaerobic: Lactate dehydrogenase (LDH)

50
Q

Where can you find high levels of malate dehydrogenase (MDH)?

A

Photoreceptors and inner plexiform layer

*photoreceptors are oxygen demanding

51
Q

Where can you find high levels of lactate dehydrogenase?

A

Mid-retina

52
Q

Where can you find low levels of lactate dehydrogenase?

A

photoreceptors

53
Q

How does the distribution (amount) of Aminotransferases in the retina compare to MDH?

A

similar to MDH

54
Q

Describe the level of TCA activity from MDH?

A

Very high TCA activity

55
Q

Where would you find areas of high oxidative enzymes?

A

Areas of low oxygen tension (i.e. high O2 usage)

e.g. photoreceptor inner segments and inner plexiform layer

56
Q

In the context of light difference, how does O2 usage compare in central vs peripheral retina?

A

Peripheral retina: less O2 in dark in outer retina, and pO2 spike in INL/GCL
Central retina: Little to no difference in outer segment (light vs dark), some in inner segment

57
Q

Describe the action of the pentose phosphate pathway in the cornea vs in the lens?

A

A larger percentage of glucose metabolism occurs through the PPP for the cornea (35%) compared to the lens (10-20%).
- this is because the lens is exposed to air more, and needs the resulting NADPH as an antioxidant