Aqueous Humor Dynamics

Aqueous humor is formed by the ciliary processes, flows from the posterior chamber through the pupil into the anterior chamber, and exits via the trabecular route at the angle and the uveoscleral route. It is being continuously formed and drained. The ciliary processes consist of about 80 processes, each of which contains a large number of fenestrated capillaries in a core of stroma. The surface of the ciliary process is covered by a double layer of epithelium: the outer pigmented and the inner non-pigmented layers. The apical surfaces of these two layers face each other and are joined by tight junctions. The epithelium double layer protrudes into the posterior chamber, providing a large surface area for aqueous secretion.

1.2.1 Theories of Production. The aqueous humor is produced by three processes: simple perfusion, ultrafiltration, and active secretion. Diffusion of solutes across cell membranes occurs down a concentration gradient. Substances with high lipid-solubility coefficients penetrate easily through biologic membranes. Ultrafiltration refers to a pressure-dependent movement along a pressure gradient. Diffusion and ultrafiltration are passive requiring no active cellular participation. They are responsible for the formation of the "reservoir" of the plasma ultrafiltrate in the stroma, from which the posterior chamber aqueous humor is derived by means of active secretion. In active secretion, energy from hydrolysis of adenosine triphos-phate (ATP) is used to secrete substances against a concentration gradient. Sodium is transported into the posterior chamber, resulting in water movement from the stromal pool into the posterior chamber.23

The identity of the precise ion or ions transported is not known, but sodium, chloride, and bicarbonate are involved. The enzymes sodium-potassium-activated adenosine triphosphatase (Na+,K+-ATPase) and carbonic anhydrase (CA), abundantly present in the nonpigmented epithelium, are intimately involved in the process of active secretion. Na+,K+-ATPase provides the energy for the metabolic pump that transports sodium into the posterior chamber, while CA catalyzes reaction of CO2 + H2O to H+ + HCO-. HCO- is essential for the active secretion of aqueous humor.

Inhibition of calcium causes a reduction of the nonpigmented epithelium intra-cellular HCO- available for transport with Na+ from the cytosol of the nonpig-mented epithelium to the aqueous, required to maintain electroneutrality. A reduction of H+ decreases H+-Na+ exchange and, again, the availability of intracellular Na+ for transport into the intercellular channel. In addition, a reduction in the intracellular pH inhibits Na+,K+-ATPase.23

1.2.2 Rate of Production. In human, the rate of aqueous humor turn over is approximately 1% to 1.5% of the anterior chamber volume per minute. The rate of aqueous humor formation is approximately 2.5 mL/min. It is affected by a variety of factors, including the integrity of the blood-aqueous barrier, blood flow to the ciliary body, and neurohumoral regulation of vascular tissue and the ciliary epithelium. Aqueous formation varies diurnally and drops during sleep.

1.2.3 Aqueous Outflow. Aqueous humor outflow consist of pressure-dependent and pressure-independent pathways. The pressure-dependent outflow refers to the tra-becular meshwork-Schlemm's canal-venous system, while the pressure-independent outflow refers to any nontrabecular outflow and is also called uveoscleral outflow.

The trabecular meshwork is divided into three layers: uveal, corneoscleral, and juxtacanalicular. The juxtacancalicular meshwork is adjacent to the Schlemm's canal and is thought to be the major site of outflow resistance. Aqueous moves both across and between the endothelial cells lining the inner wall of Schlemm's canal. A complex system of channels connects Schlemm's canal to the episcleral veins, which subsequently drain into the anterior ciliary and superior ophthalmic veins.

In the uveoscleral pathway, the predominant route appears to be the aqueous passage from the anterior chamber into the ciliary muscle, and then into the sup-raciliary and suprachoroidal spaces. The fluid then exits the eye through the intact sclera or along the nerves and the vessels that penetrate it. The reasons for the pressure independence of this pathway are not entirely clear but might be consequent to the complex nature of the pressure and resistance relationships between the various fluid compartments within the soft intraocular tissues along the route.23,24

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