Aqueous Humor Formation and Secretion

The ciliary epithelium is a bilayer of polarized epithelial cells that line the surface of the ciliary body. The 2 cell layers are the nonpigmented epithelium (NPE), which faces the aqueous humor, and the pigmented epithelium (PE), which faces the ciliary stroma. These 2 layers are connected to each other at their apical membranes; their basal membranes face the aqueous and ciliary stroma. The NPE has tight junctions proximal to the apical plasma membrane that form part of the blood–aqueous barrier, thereby preventing paracellular transport from the ciliary stroma into the posterior chamber. In contrast, the PE cell layer is considered a leaky epithelium because it allows solutes to move through the space between the PE cells.

Aqueous humor is secreted by the NPE from a substrate of blood plasma. It is secreted at a flow rate of 2–3 µL/min, but this rate varies according to our circadian rhythm, dropping to 1.0 µL/min at night.

Aqueous enters the posterior chamber from the ciliary processes by means of active and passive physiologic mechanisms:

• active: energy-dependent secretion of certain ions and substrates

• passive: diffusion and ultrafiltration

The active process of aqueous secretion involves enzymes present in the NPE, such as sodium-potassium adenosine triphosphatase (Na⁺,K⁺-ATPase) and carbonic anhydrase (CA). Active secretion of sodium by Na⁺,K⁺-ATPase and accompanying anions creates high osmolarity on the basolateral (aqueous) side of the NPE, and this in turn promotes diffusion of water. In humans, CA is present in both PE and NPE. Its inhibitors reduce the rate of entry of sodium and bicarbonate into the aqueous, causing a reduction in aqueous flow. See Chapter 16 for further discussion.

Cotransport is the coupled transport of 2 chemical substances across a membrane, with one substance transported down its concentration gradient, which drives movement of the other substance against its concentration gradient. Symport and antiport are cotransport mechanisms. Symporters are membrane proteins that mediate the cotransport of molecules in the same direction, whereas antiporters mediate the cotransport of molecules in opposite directions. The systems’ activities and cellular distributions along the membranes of PE and NPE cells determine unidirectional net secretion from the ciliary stroma to the posterior chamber, a process that involves 3 steps (Fig 9-1):

1. uptake of solute and water at the stromal surface by PE cells

2. transfer of solute and water from PE to NPE cells through gap junctions

3. transfer of solute and water by NPE cells into the posterior chamber

Likewise, it is thought that there is a mechanism for transporting solute and water from the posterior chamber back into the stroma. In this unidirectional reabsorption, another set of transporters may be involved in extruding sodium, potassium, and chloride back into the stroma.

Diffusion is the movement of solutes or ions across a membrane down the concentration or ionic gradient. In aqueous formation, ultrafiltration is the nonenzymatic component that depends on intraocular pressure (IOP), blood pressure, and the blood osmotic pressure in the ciliary body. Ultrafiltration decreases with increasing IOP.

IOP is maintained by continuous aqueous formation and drainage, which allow removal of metabolic waste products from the surrounding tissues. The factors determining IOP are summarized in the Goldmann equation and include

• rate of aqueous production

• resistance to outflow

• the pressure within the episcleral veins receiving drainage from the Schlemm canal

Figure 9-1 Production and secretion of aqueous humor. The oncotic pressure of the ciliary body stroma draws water toward the stroma from the neighboring blood vessel but also away from the posterior chamber. Thus, energy-dependent mechanisms (active transport) are needed to secrete water across the ciliary epithelium. This is accomplished by sodiumpotassium adenosine triphosphatase (Na⁺,K⁺-ATPase), which pumps Na⁺ into the posterior chamber. The resultant increase in osmolarity draws water into the posterior chamber via aquaporin channels. Within the epithelial layers, carbonic anhydrase provides hydrogen ions (H⁺), which are exchanged with Na⁺ to help provide a supply of sodium within the epithelium and drive the flow of water. Adrenergic stimulation has been reported to drive Na⁺,K⁺-ATPase. 1, Na⁺,K⁺ antiport; 2, K⁺ channel; 3, Cl⁻ channel; 4, Na⁺,H⁺ antiport; AqPO1 = aquaporin channel 1.

(Adapted with permission from Forrester JV, Dick AD, McMenamin PG, Roberts F, Pearlman E. The Eye: Basic Sciences in Practice. 4th ed. Edinburgh: Elsevier; 2016:224, Box 4-14.)

Inhibitors of enzymatic processes decrease aqueous inflow by varying amounts, providing additional evidence of active secretory processes. For more information, see Chapter 16 of this volume and BCSC Section 10, Glaucoma.

Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.