Aqueous Humour Dynamics

• Anterior chamber volume: 250μL (average depth is 3.1mm)
• Posterior chamber volume: 60μL
• Normal intraocular pressure is generally 10-20mmHg (with a positive skew)
• Aqueous is the main nutrient source for the avascular lens and cornea
• Lower glucose than plasma
• Low protein
• High ascorbate

• Aqueous is secreted by the non-pigmented (inner) ciliary body epithelium into the posterior chamber, utilising the active transport of sodium via the Na/K ATPase pump

• Produced via (see above)
• Active secretion (70%)
• Ultrafiltration (20%)
• Osmosis (10%)
• Factors affected IOP:
• Circadian rhythm
• Episcleral venous pressure
• Rate of secretion
• Rate of flow
• Neural and hormonal influences

Neural control

• Adrenergic and cholinergic receptors are present in the iris and CB
• Alpha2 receptors are the most abundant in the ciliary body

• Adrenergic receptors (and muscarinic receptors) are present in the ciliary epithelium. Note: adrenergic receptors regulate IOP via adenylate cyclase (a G-protein driven process)

• Beta-adrenergic ANTAGONISTS suppress flow (eg. timolol)

• Beta-adrenergic stimulation increases aqueous secretion by activating adenylate cyclase

• Alpha2-selective adrenergic agonists suppress flow (eg. clonidine)
• Inhibition of adenylate cyclase

• Cholinergic mechanisms are not involved in IOP control (despite the effect of pilocarpine in reducing IOP…)

Circadian regulation

• Melatonin has IOP-lowering effects and may therefore produce the diurnal variation in IOP.

• IOP highest in the morning
• Secretion falls to 1ml/minute at night (from 2.6ml/min during the day)

Outflow

• Conventional: trabecular meshwork
• Pressure dependent

• Resistance to outflow here occurs at the level of the TM endothelium and within the matrix of the meshwork

• The juxtacanalicular cribiform meshwork accounts for the greatest resistance into Schlemm’s canal

• These endothelial cells have mechanosensor/stretch receptors to regulate the formation of transcellular pores

• Aqueous is transported via transcytosis: water-containing vesicles move through micron-sized pores across the meshwork to Schlemm’s canal (giant vacuoles)

• The endothelial cells have active phagocytic properties and are specialised for endocytic transport and contractility. 

• Also produce the TM matrix components
• TM cells have adrenergic receptors and glucocorticoid receptors

• Glucocorticoids induce the expression of trabecular meshwork inducible glucocorticoid response protein (TIGR).

• Mutations in TIGR gene (myocillin gene) are found in glaucoma

• Uveoscleral: 10-40% of aqueous drainage
• Pressure independent

• Direct drainage into the anterior uvea at the CB (through gaps in the endothelial lining here) and then into the suprachoroidal space

• MMP-1 may contribute to uveoscleral drainage
• Pressure in the suprachoroid is 2-4mmHg lower than in the AC 

• Prostaglandins predominantly increase uveoscleral outflow to lower IOP
• Estimated at 0.3μL/minute

• Episcleral drainage

• Schlemm’s canal has direct vascular communication with a network of intrascleral collector channels

• These drain into scleral veins
• Normal episcleral venous pressure is 8-10mmHg