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What causes the leak of water from aqueous into the corneal stroma?
IOP through leaky tight junctions
What causes fluid to leave the stroma to the aquoeus?
corneal endothelial pumps
T or F, the relationship between corneal hydration and thickness is linear
T
What happens if rate of leak is greater than pump function?
corneal swelling
What happens when pump rate exceeds the leak rate of water from cornea?
corneal deturgescence
Overall, what moves transcellularly through the corneal endothelium?
HCO3- and Cl-
Overall, what moves paracellularly through the corneall endothelium?
Na+ and H2O
What sets up concentration gradient of higher sodium in the stroma?
NK ATPase
What does NBC do?
Sodium Bicarbonate Co-transporter brings in 1 Na+ and 2 HCO3- into endothelial cell
What removes hydrogen from the endothelial cell?
NHE Na+ H+ Exchanger
What brings in chloride into the corneal endothelium?
Anion Exchanger and NKCC (Co-transporter)
What converts bicarbonate acid to CO2 and H2O to allow bicarbonate acid to build up outside the cell?
Carbonic Anhydrase II
How does CO2 go from intracellular to the anterior chamber?
diffusion
How does CO2 get converted to bicarbonate in the anterior chamber?
Carbonic Anhydrase IV and water in anterior chamber
What happens to the elevated chloride concentration in the corneal endothelial cell?
Cl- leaves through Calcium Activated Chloride Channels and CFTR
What is the function of building up chloride and bicarbonate in the anterior chamber?
The high negative charge draws Na+ paracellularly into the anterior chamber, and water follows
How is water drawn into the cell?
osmosis following Na+ drawn by the electrostatic gradient of Cl- and HCO3-
Why is there a high lactate concentration in the corneal stroma?
Byproduct of the metabolism/high energy requirements of the corneal endothelium
What transports lactate from stroma into the endothelial cell and then the anterior chamber?
MonoCarboxylate Transporters
What protein makes up tight junctions?
claudin
What determines the ‘leakiness’ of an epithelium?
Differential claudin expression, the pores it forms to allow ion and water movement
What might lead to increased endothelium ion transport?
injury and changes in cell volume
Activation of what 2 transportaion mechanisms occurs with stimulation?
CaCC via increasing intracellular Ca2+
Purinergic receptors (activated by ATP) → increase in intracellular cAMP → activation of CFTR
What autonomic system do lacrimal acinar and duct use?
parasympathetic
T or F, water move both paracellularly and transcellularly
T, aquaporins mediate a transcellular movement, but water movement is predominantly paracellular
CHED
Congenital Hereditary Endothelial Dystrophy: NBC co-transporter function disrupted (due to mutation in gene SLC4A11) → corneal edema
Why is there some edema in premature infants?
Corneal pump mechanism (NKA…) is not fully developed yet
When do babies’ corneas reach normal adult hydration?
about 20 days after normal birth
With age, density of corneal endothelial cells (increases or decreases)?
decreases
How does endothelial pump change with age
it doesn’t really
Why don’t we get corneal edema with age?
NKA can increase number and activity to compensate for cell loss; leak > pump
What could cause endothelial cell loss?
CLs, crosslinking therapy, refractive and cataract surgery, trauma, corneal transplants
When might we get corneal edema (by losing pump function) with age?
with pathological causes like surgery, trauma, contact lenses…
