Retinal Metabolism - Week 5 Flashcards
For what processes in the body is ATP usage the highest?
- Dark current
- Neurotransmission
- Ionic Transport
- cGMP, GTP production
What is the metabolic role of NADPH (a reductin)?
is used in:
- chromophore recycling
- membrane synthesis
- as an antioxidant
- membrane integrity + photopigment function
- RNA synthesis/DNA repair
- Vasomotor regulation
What is the metabolic role of Ribose-5-Phosphate?
is used in RNA synthesis
Where in the rod photoreceptor does Rhodopsin de-activation occur?
Outer segment
Where in the rod photoreceptor is rhodopsin found?
Outer segment
Where in the photoreceptor does cGMP synthesis occur?
Outer segment
What is the main role of the photoreceptor inner segment?
Provide ATP for the sodium potassium pump
What is the main role of the photoreceptor outer segment?
Absorption of light
Where in the photoreceptor does phototransduction occur?
Outer segment
Briefly describe the outer segment of a photoreceptor
are actually modified cilia that contain discs filled with opsin (the molecule that absorbs photons), and has voltage gated sodium channels
Where in the photoreceptor does RNA synthesis take place?
Inner segment
What results from impaired transport or defective proteins in the inner segment of the photoreceptor?
Some form of retinal degeneration e.g. RP
What pathway is the primary source of NADPH?
Pentose Phosphate Pathway
Where does glucose get stored?
In the muscle
Note: it does NOT get stored in the brain or retina
What is the main product of Glycolysis?
Precursors that feed kreb cycle (and a little bit of ATP as well)
Briefly describe the Kreb/TCA cycle
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
What happens when you break a carbon off a molecule in the Kreb/TCA cycle?
you generate a reductin (either NADH or FADH)
How do reductins help generate ATP?
When added to the ETC, reductins can drive an electron gradient to create ATP
What happens to the amino acids produced by the Kreb/TCA cycle?
They become our Neurotransmitters
What 2 things provide vascular supply to the two halves of the iris?
Minor arterial circle - bottom half
Aqueous - top half
Where does the ophthalmic artery originate from?
Internal carotid artery
Where do the the short posterior ciliary arteries enter the eye?
They pierce the sclera posteriorly to enter the choroid layer
Where do the long posterior ciliary arteries enter the eye?
travel medially and laterally along the sides of the optic nerve and past the anterior aspect of the eyeball, piercing the choroid layer
Which part of the retina does the central retinal artery supply?
internal surface of the retina (it pierces close to the optic nerve)
What supplies the outer layer of the retina?
Choroidal vessels (choriocapilaris)
What supplies the inner layer of the retina?
Retinal vessels and their capillaries
Where in the posterior segment of the eye is oxygen tension maximal?
Choriocapillaris
Compare the autoregulation of the blood supply to the outer and inner retina. Where does it occur?
Inner layers of retina = locally autoregulated (via myogenic + metabolic mechanisms)
Outer layers of retina = NO local autoregulation
Compare the flow rate for the outer and inner retina. Where is it highest?
Outer retina = Very high flow rate
Inner retina = Low flow rate
Compare the venous oxygen saturation for the outer and inner retina? Where is it highest?
Outer retina = High venous oxygen saturation
Inner retina = Low venous oxygen saturation
Define autoregulation
Intrinsic ability to maintain a constant blood flow despite changes in perfusion pressure
How does autoregulation compensate for low blood pressure?
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)
How does autoregulation compensate for high blood pressure?
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.
Define sheer stress
The dragging force of the blood on the vessel wall
When is oxygen tension lower, in the dark or light?
Oxygen tension is lower in the dark. O2 is being consumed in dark current
How much O2 is generally utilised by the retina per hour?
1.5umol/mg dry weight/hour
Which uses more oxygen: retina or brain?
Retina (2x more than brain)
Where is oxygen used in the retina?
70% of O2: TCA cycle, glycolysis, oxidative phosphorylation
Remainder of O2: oxidation of pyruvate, lactate, amino acids
What mechanism actively transports glucose across membranes?
Na+/Glucose symports
What mechanisms passively transport glucose across membranes?
Glucose transporter (GLUT) family. 5 types: GLUT1-5. GLUT-1 most important.
are ‘uniports’
What are the normal glucose levels in serum?
4-8mM
is ATP excitatory or inhibitory for GLUT-1
inhibitory
at what serum glucose level does GLUT-1 operate at 50% efficiency?
1mM
Where is GLUT-1 found
Basically everywhere in the retina. Anything that’s brown
Where is GLUT3 found?
Inner retina
Where is GLUT-2 found?
Only found in ELM and ILM (External and Internal limiting membrane)
*it’s a muller cell glucose transporter
What what serum glucose levels does GLUT-2 operate at 50% efficiency?
15mM
Where is GLUT-4 and GLUT-5 found?
Nowhere in the retina
What can you use as an indicator of the level of oxygen usage in an area of the retina?
The level of certain aerobic vs anaerobic enzymes
Aerobic: Malate dehydrogenase (MDH) and Glutamate dehydrogenase (GDH)
Anaerobic: Lactate dehydrogenase (LDH)
Where can you find high levels of malate dehydrogenase (MDH)?
Photoreceptors and inner plexiform layer
*photoreceptors are oxygen demanding
Where can you find high levels of lactate dehydrogenase?
Mid-retina
Where can you find low levels of lactate dehydrogenase?
photoreceptors
How does the distribution (amount) of Aminotransferases in the retina compare to MDH?
similar to MDH
Describe the level of TCA activity from MDH?
Very high TCA activity
Where would you find areas of high oxidative enzymes?
Areas of low oxygen tension (i.e. high O2 usage)
e.g. photoreceptor inner segments and inner plexiform layer
In the context of light difference, how does O2 usage compare in central vs peripheral retina?
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
Describe the action of the pentose phosphate pathway in the cornea vs in the lens?
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
