Biochem- Metabolic Eye Flashcards
What 2 subtances composes the cornea?
Collagen type I and proteoglycans
What if there is an accumulation of GAGs in the cornea?
Cleauding
What type of metabolism does the corneea use to get energy (aerobic or anaerobic)?
Anaerobic mainly
Energy comes from which substance since the cornea is anaerobic?
Aqueous humor
What are the 2 things that make up the lens?
water and crystallin proteins
What is the fxn of crystallin proteins?
increase transparency
What type of metabolism does the lens use to get energy (aerobic or anaerobic)?
Anaerobic
Is the retina part of the CNS or PNS?
CNS
The retina has a pretty good vascular supply except where?
The fovea
What type of metabolism does the retina use to get energy (aerobic or anaerobic)?
Mostly anaerobic metabolism but also oxidative metabolism because it is much more efficient
Wearing contacts cuts off what supply?
Oxygen diffusion to the cornea
Cutting off O2 supply causes what metabolic changes?
increase in lactate and decrease in pH
The increase in lactate and decrease in pH cause what changes to the cornea?
lactate causes corneal swelling –> increased thickness and disruption of fiber arrangement –> cloudiness
(lol great thing I wore contacts for 10 years)
What is the chemical composition of aqueous humor?
Na+, bicarbonate, Cl-, glucose, amino acids, and ascorbic acid
Is aqueous humor free flowing?
yes
What are the 2 roles of aqueous humor?
Brings: nutrients to the cornea and lens
Removes: end products from the cornea and lens to the blood stream
What is the chemical composition of vitreous humor?
99% water, type II collagen, proteoglycans (chondroitin sulphate), and hyaluronic acid
Is vitreous humor free flowing?
Nope
What is the role of vitreous humor?
Keep the retina in palce
What 2 things does the eye depend on for antioxidants?
The eye depends on both ascorbic acid (vitamin C) and reduced glutathione to prevent and/or reverse photo-oxidation
How do we get vitamin C?
;-)
Which molecule is needed to regenerate reduced glutathione?
NADPH
True or False: Glaucoma is an increase in intra-ocular pressure, causing damage to the eye.
FALSE
So what is glaucoma?
Glaucoma is an eye disease in which the optic nerve is damaged. It is NOT synonymous with increased intra-ocular pressure because there can be normal or low tension glaucomas as well. Increased intra-ocular pressure, however, is the most common cause of glaucoma.
What causes an increase in intra-ocular pressure?
a decrease in drainage (as seen with primary open angle glaucoma, the most common form)
Who are the patient populations most prone to cataract formation?
Diabetics and galactosemic infants
What are the 3 mechanisms to cataracts?
osmotic, oxidation, and modification of proteins.
What causes formation of cataracts through osmotic changes?
. Sugars are reduced to sorbitol –> sorbitol causes osmotic uptake of water which hydrates crystallins (which are normally dehydrated and found on the surface of the lens in order to increase transparency) –> hydrated crystallins aggregate (cataract formation) and scatter light.
What causes formation of cataracts through oxidation changes?
sugars are oxidized to produce dicarbonyl compounds which oxidizes glutathione and inhibits the pentose pathway which is used to produce NADPH, a coenzyme of glutathione reductase –> protein aggregation
What causes “wet” AMD?
caused by the growth of blood vessels underneath the macula and then rupturing because they are fragile
What causes “dry” AMD?
a slow break down of the macula and yellow deposits known as drusens are left behind
So what are the main differences between wet and dry AMD on clinical exam?
Wet AMD is acute, more serious, and rapidly progressing. It can also cause complete vision loss within a few days. Although it is the more serious form of AMD, it can be treated with an injection of VEGF inhibitors.
Dry AMD on the other hand progresses very slowly and generally only impairs vision. It cannot be treated
I’m now gonna copy/paste some Q&A’s from ray’s section of the module. There are repeats.
What is the major fuel of the eye?
Glucose
In the lens and cornea, how is most of the ATP produced?
By anaerobic glycolysis
In the retina, how is ATP produced?
By both anaerobic glycolysis and oxidative metabolism.
Why is there little or no oxidative metabolism in the lens or cornea?
Blood vessels and mitochondria absorb light and interfere with vision.
What are the layers of the cornea?
From the outermost layer to innermost: ABCDE (Anterior (corneal) epithelium, Bowman’s layer, Corneal stroma, Descemet’s membrane, and Corneal Endothelium)
What syndromes cause corneal clouding?
Hurler (MPS I) and Sly (MPS VII) syndromes due to the accumulation of glycosaminoglycans.
What is the normal water content of the cornea?
78%
How is this water content maintained?
Active pumping of HCO3- out of the cornea.
How do GAGs cause clouding?
GAGs increase water uptake disrupt fiber arrangement
How is clarity sustained in the cornea?
Large amounts of VEGFR-3 in the anterior epithelial layer
What is the function of VEGFR-3?
Prevents growth of blood vessels by binding to and neutralizing growth factors that stimulate angiogenesis.
Why is ATP important?
Mainly ion transport for transparency.
How is glucose used in the cornea?
40% glycolysis (35% anaerobic, 5% oxidative glycolysis) 60% pass through the pentose phosphate pathway to produce NADPH (used to prevent or reverse photo-oxidation w/ reduced gluthathione).
Why do we need an anti-oxidant system?
Large amounts of oxygen via diffusion allows for photo-oxidation in the cornea and lens.
What is the function of NADPH in this anti-oxidant system?
NADPH is the coenzyme of glutathione reductase which is used to keep glutathione reduced.
Why are tears important?
It provides the cornea (which is avascular) with oxygen via diffusion.
What is the effect of prolonged wearing of contact lenses?
Hypoxic conditions underneath the lens (↑lactate and ↓corneal pH)
What is the effect of increased lactate?
It will diffuse from the epithelium into the stroma and cause corneal swelling due to osmosis.
What is the function of the aqueous humour?
It maintains the intra-ocular pressure, brings nutrients (mostly glucose, amino acids, and ascorbic acid via facilitated diffusion or active transport) to the cornea and lens, and removes end products to the blood stream.
Where does the aqueous humour come from?
Secreted by ciliary processes into the posterior chamber.
How does the aqueous humour flow?
Posterior chamber pupil anterior chamber trabecular meshwork Schlemm’s canal.
What is the vitreous humour?
Non free flowing gelatinous mass made up of 99% water held together by collagen type II, proteoglycans (mainly sulphate), and hyaluronic acid.
What is the function of the vitreous humor?
To keep the retina in place.
What is posterior vitreous detachment (PVD)?
A common and normal cause of occasional flashing lights and floaters in the visual field.
What causes PVD?
With age, the vitreous humour becomes more liquid-like increasing the risk of separation from the retina.
When is PVD serious?
Frequent flashing and floaters indicate retinal detachment and requires immediate attention.
What is glaucoma?
Optic nerve damage.
What is the main cause of glaucoma?
Increased intra-ocular pressure.
What normally causes an increase in intra-ocular pressure, increased aqueous humor production or a decrease in drainage?
Decrease in drainage.
What is the most common form of glaucoma?
Primary open angle glaucoma
Africans are most susceptible to which form of glaucoma, open angle or closed?
Open.
What is it most commonly treated with?
Prostaglandin analogs which increase drainage (latanoprost (XALATAN) or B-blockers which reduces the secretion of aqueous humour (timolol (TIMOPTIC) or betaxolol.
What is used to treat acute attacks?
Cholinergic agonists such as pilocarpine which restores resorption and outflow of aqueous humour.
How do carbonic anhydrase inhibitors work?
They decrease the rate of bicarbonate production decrease aqueous humour secretion.
What are some carbonic anhydrase inhibitors?
Acetazolamide (DIAMOX), methazolamide (NEPTAZANE), and dorzolamide (TRUSOPT, used topically only).
What is a combination of B-blocker and carbonic anhydrase inhibitor used frequently?
COSOPT which is timolol and dorzolamide.
What is closed-angle glaucoma?
Less common form of glaucoma in which the outer edge of the iris protrudes over the drainage canal.
How is closed-angle glaucoma treated?
By surgically removing the outer edge of the iris.
What are risk factors for glaucoma?
Africans (primary open angle), family history, diabetes, myopia, >45 y/o, prolonged steroid use, eye injury (secondary glaucoma).
What is secondary glaucoma?
Glaucoma with an identifiable cause of increased optic pressure (injury, steroid use)
What is the lens made up of?
Mostly water and proteins
What separates the aqueous humor from the vitreous humor?
The lens.
What brings the avascular lens nutrients and removes wastes?
The aqueous humor.
Where does protein synthesis take place on the lens?
The periphery
Are these proteins, , and crystallins, normally hydrated or dehydrated?
Dehydrated.
What is the function of these proteins?
They increase transparency with increased concentration but too much decreases transparency (cataract formation).
Besides reduced glutathione (~20mM), what is another important anti-oxidant?
Ascorbic acid (~2 mM)
