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What is the embryological source of the pigmented and non-pigmented epithelium of the ciliary body?
ectoderm
What is the embryological source of the vasculature of the ciliary body?
mesoderm
What is the embryological source of post/ant epithelial cells of the iris?
distal tip of the optic vesicle (ectoderm)
What is the embryological source of stroma of the iris?
neural crest/ectoderm
What is the embryological source of iris vasculature?
mesoderm
What is the embryological source of choroid vasculature?
mesoderm
What is the embryological source of ciliary muscle?
neural crest/ectoderm
What is the embryological source of trabecular meshwork?
neural crest/ectoderm
What is the embryological source of Schlemm's canal?
mesoderm
aniridia
congenital lack of the iris and disruption of anterior segment
most known cause is due to mutation of the Pax6 gene
at risk for developing
Why is aqueous humor composition different than that of blood plasma?
due to the blood-aqueous barrier
What are the differences between the aqueous humor composition and blood plasma?
protein content: blood plasma protein concentration is greater in the aqueous humor
ascorbic acid/ascorbate: concentration is greater in the aqueous humor than plasma
lactate: concentration is higher in aqueous humor than plasma
What are the major ions found in the aqueous humor?
sodium chloride
bicarbonate lactate
What is the most prevalent ion in the aqueous humor?
sodium
What organic molecules are present in aqueous humor?
ascorbate
urea
glucose
lactate
Which has lower pH: aqueous humor or plasma?
aqueous humor
What are the two processes that produce aqueous humor?
ultrafiltration
ion/water secretion
ultrafiltration
produces a reservoir of plasma in the ciliary process stroma
IOP sensitive
ion/water secretion
moves ions from plasma ultra filtrate to aqueous humor
transport of ions occurs bilayered ciliary epithelium
IOP sensitive
capillary hydrostatic pressure
pushes fluid from capillaries through fenestrations into the stromal space in a process called ultrafiltration
capillary derived solution is referred to as the "ultrafiltrate"
created by fenestrations of stroma
What causes ultrafiltration?
solution movement across a semi-permeable barrier due to pressure differential
balance between oncotic and hydrostatic pressures
What is ultrafiltration opposed by?
IOP and oncotic forces
What must happen for ultrafiltration to occur?
hydrostatic pressure must be larger than the sum of the IOP + oncotic pressure
Is ultrafiltration sensitive to IOP?
yes
as IOP rises ultrafiltration decreases
decrease in facility of inflow
a decrease in ultrafiltration due to IOP
What happens to ultrafiltration if capillary pressure drops below a critical level?
ultrafiltration will not occur because ultrafiltration cannot overcome both oncotic pressure and IOP
What happens to ultrafiltration if IOP increases to a critical level?
ultrafiltration will also be inhibited
What is the relationship between blood flow/aqueous humor production?
when the blood flow is in the range of normal to 75% below normal, production of aqueous humor is independent of bloodfloow
when blood flow is significantly below normal, production of aqueous humor is dependent on blood flow and is also reduced
What is aqueous humor production under physiological conditions?
2.5 ul/min
How is aqueous humor production affected by IOP at normal levels?
it is unaffected
How is aqueous humor production affected when IOP is very high?
aqueous humor production decreases due to exceeding ability of blood flow to be auto regulated
T/F: aqueous humor production is an energy dependent process
true, it is dependent on oxygen levels and therefore requires aerobic metabolism
What does the basolateral domain of the pigmented ciliary process epithelium face?
ciliary process stroma
What does the basolateral domino of the the non-pigmented ciliary process epithelium face?
faces the aqueous humor
Where are non-leaky tight junctions found in the ciliary processes?
found only in non-pigmented epithelium
Where are gap junctions are found in the ciliary processes?
found between the pigmented epithelium cells
between non-pigmented epithelium cells, and between pigmented epithelium and non-pigmented epithelial cells
What are the functions of gap junctions in aqueous humor secretion?
gap junctions allow free diffusion of ions and water between epithelial layers
What is the stroma ultra filtrate sodium concentration compared to that of intracellular concentrations?
ultra filtrate has a high sodium concentration relative to intracellular concentrations
What prevents paracellular transport in the ciliary processes?
tight junctions
Where are aquaporins found in the ciliary processes?
both in the non-pigmented and pigmented ciliary epithelium
How is glucose transported across the ciliary epithelia?
transported through sodium dependent SGLT and independent mechanisms
SGLT
transports glucose into cells from the ciliary process stroma using sodium concentration gradient
GLUT
glucose exits through facilitated diffusion
Where are GLUTs found in ciliary processes?
found in non-pigmented epithelial cells
What is the function of ascorbate in the aqueous humor?
absorb UV light
donates electrons to ROS
What two molecules scavenge for ROS in the aqueous humor?
ascorbate
urea
What is the rate of aqueous humor formation?
2.5 microliters/min
T/F: aqueous humor production is reduced at night?
true
How is the circadian rhythm of aqueous humor controlled?
controlled by autonomic/adrenergic control
Where are the cell bodies of the parasympathetic fibers that are associated with the ciliary epithelium and ciliary blood vessels?
cell bodies of postganglionic parasympathetic fibers originate in the pterygopalatine ganglion
What sympathetic fibers innervate the blood vessels of the ciliary body?
postganglionic fibers from the superior cervical ganglion
How does binding of agonists to B adrenergic receptors affect the ciliary epithelium,?
this triggers the formation of cAMP which in turn directly activates chloride channels
activation of chloride channels increases aqueous humor formation and increases IOP
What is the mechanism of action for timolol?
Beta receptor antagonist which prevents normal levels of stimulation which maintain the activation of chloride channels
lack of chloride channel activation decreases aqueous humor formation and decreases IOP
How does simulation of adenosine receptors cause a higher IOP?
stimulation of A3 adenosine receptors triggers the activation of chloride channels which lead to more aqueous humor production and a higher IOP
What are the two mechanisms by which alpha 2 agonists decrease aqueous humor formation?
1. presynaptic nerve inhibition (systemic application)
2. direct inhibition of non-pigmented cell secretion (topical application)
clonidine
alpha 2 agonist that inhibits presynaptic sympathetic nerves
Apraclonidine/brimonidine
alpha 2 agonist that directly inhibits NPE cell secretion
What is the mechanism of action of clonidine?
alpha 2 receptor present in the presynaptic sympathetic nerve inhibits further norepinephrine release and block further synaptic transmission
vasodilation ensues due to reduced smooth muscle contraction
lowers aqueous humor production
What is the mechanism of action of apraclonidine/brimonidine?
alpha 2 receptors are present in ciliary epithelium and stimulation of them causes reduction of intracellular cAMP
reduction in cAMP reduces basolateral ion transport (Cl-)
What is the mechanism of action of dorzolamide and brinzolamide?
inhibition of carbonic anhydrase which indirectly reduces ion transport and therefore reduces aqueous humor production