Aqueous Humor Formation

Formation of the aqueous humor

aqueous humor is secreted by the ciliary epithelium and circulates over the lens and through the pupil, i.e., it is found in the anterior and posterior chambers
similar in composition to protein-free plasma
normal volume is ~125 µL; pressure ~20 mm Hg
there are two pharmacologically important components of formation (inflow):
1. sympathetic nervous system
  - stimulation of β₂ receptors by circulating epinephrine increases flow by increasing [cAMP]
  - stimulation of α₂ receptors by norepinephrine reduces production by decreasing [cAMP]
2. increased Cl^- secretion by the ciliary epithelium produces an increase in aqueous humor volume via osmosis
  - generation of bicarbonate by carbonic anhydrase regulates Cl^- secretion

drainage (outflow) also occurs via two systems (although the mechanisms are more controversial):

canal of Schlemm (primary mechanism): contraction of the sphincter pupillae muscle (which results in miosis) moves the iris away from the canal, increasing outflow
- administration of muscarinic antagonists or sympathetic α₁ agonists (both of which can dilate the pupil) can exacerbate glaucoma, by reducing drainage of the aqueous humor

uveoscleral outflow: reabsorption of aqueous humor through the ciliary muscle is increased by muscle relaxation and facilitated by prostaglandins (specifically PGF_2α), which represent an important mechanism of glaucoma treatment
- the specific mechanism of action of prostaglandins is unknown
  - a recent review of uveoscleral flow indicated that relaxation of the ciliary muscle was the principal mechanism of action of prostaglandins
  - there are data that indicate that prostaglandins work by “dissolving” connective tissue (in a similar manner to what they do to the cervix during labour)
- although parasympathetic stimulation causes contraction of the ciliary muscle (see accomodation) and should therefore decrease drainage, it's thought that these harmful parasympathetic actions are offset by an increase in flow through the canal of Schlemm

Bottom line: both cholinergic agonists and prostaglandins are both used to treat glaucoma, and they work by increasing outflow