Aqueous humor formation

Function of aqueous humor

Aqueous humor was originally thought to be stagnant. It was not until 1921 that Seidel proved that the aqueous was, indeed, circulating. Using a needle, Seidel connected a reservoir containing a blue dye to a rabbit eye. When the reservoir was lowered, clear fluid from the anterior chamber entered the tubing; when the reservoir was raised, the dye entered the eye and eventually appeared in the blood of the episcleral venous plexus.1,2 Seidel concluded that aqueous humor must be continuously formed and drained. Two decades later, Ascher showed that aqueous humor enters the venous system at the limbus through the aqueous veins and first flows alongside the bloodstream in a laminar fashion before mixing completely with the blood in the veins.3 Ashton studied neoprene casts of Schlemm’s canal and the aqueous veins and demonstrated a direct connection between these two structures.4 From the work of the last half century it is clear that aqueous humor is a relatively cell-free, protein-free fluid that is formed by the ciliary body epithelium in the posterior chamber. It then passes between the iris and the lens, enters the anterior chamber through the pupil, and exits the eye at the anterior chamber angle through the trabecular meshwork, Schlemm’s canal, and the aqueous veins. In the anterior chamber, the aqueous humor is subject to thermal currents because of the temperature difference between the iris and the cornea; aqueous rises close to the warmer iris and descends close to the cooler cornea. This convection current may easily be seen clinically when there are cells or pigment in the anterior chamber, and explains the relatively inferior location of pigment deposition (Krukenberg spindle) and keratic precipitates on the inner surface of the cornea.

During its passage through the eye, the aqueous humor serves a number of important functions. It serves in lieu of a vascular system for the normally avascular structures of the eye, including the cornea, lens, and trabecular meshwork. It brings to the internal eye essential nutrients, such as oxygen, glucose, and amino acids,5 and removes metabolites and potentially toxic substances, such as lactic acid and carbon dioxide.6,7 Aqueous humor provides the proper chemical environment for the tissues of the anterior segment of the eye and provides an optically clear medium to allow good visual function. It inflates the globe and maintains intraocular pressure (IOP), both of which are important for the structural and optical integrity of the eye. In many species, including humans, aqueous humor contains a very high concentration of ascorbate, which may act to scavenge free radicals and protect the eye against the effects of ultraviolet and other radiation. Under adverse conditions (e.g., inflammation, infection), it facilitates cellular and humoral immune responses. During

inflammation, the rate of aqueous humor formation decreases, and its composition is altered to permit accumulation of immune mediators (Box 2-1).

Several risk factors probably contribute to damaging the optic nerve with its resultant visual loss in glaucoma. Intraocular pressure that is too high for the continued health of the nerve is universally accepted as one of the most important of those risk factors. Therefore the study of those elements that contribute to the creation, maintenance, and variation of IOP is material to the understanding of the pathophysiology of this disease. Aqueous formation (F), facility of outflow (C), and episcleral venous pressure (Pv) are the major intraocular determinants of IOP. These factors are related to one another by the Goldmann equation:

PO F/C Pv

or if solving for F:

F (PO Pv )C

in which PO is the IOP in the undisturbed eye in mmHg, aqueous formation is in l/min, the facility of outflow is in l/min/mmHg, and the episcleral venous pressure is in mmHg. From the equation, it is evident that IOP will increase when the aqueous formation rate increases, the episcleral venous pressure increases, or the outflow facility decreases. More recently, with the discovery of a pressure-independent outflow mechanism(s) (the uveoscleral pathway being the main one), the equation has had to be modified and is better stated:

F (PO Pe )C U

where Pe is the sum of the external pressure such as episcleral venous pressure and other tissue pressures outside the eye, and U is the sum of the pressure-independent outflow pathways.8

Box 2-1  Functions of aqueous humor

Brings oxygen and nutrients to cells of lens, cornea, iris

Removes products of metabolism and toxic substances from those structures

Provides optically clear medium for vision

Inflates globe and provides mechanism for maintaining intraocular pressure

High ascorbate levels protect against ultraviolet-induced oxidative products, e.g., free radicals

Facilitates cellular and humoral responses of eye to inflammation and infection