Essentials of Veterinary Ophthalmology. Kirk N. Gelatt

globe. AH is a clear, colorless liquid that fills the anterior and posterior chambers as well as the pupil. It has a refractive index of 1.335, which is slightly denser than water, and is a critical constituent of the eye's optical system. As AH is formed by the ciliary body processes, it enters the posterior chamber and flows through the pupil into the anterior chamber, where it leaves the eye through the corneoscleral trabecular and uveoscleral outflow pathways. The rate of AH formation equals the outflow, so the IOP is maintained relatively constant, and the refractive surfaces of the eye are kept in a normal position.

      This continuous flow of AH supplies the avascular cornea and lens with nutrients and also removes their waste products. A convection current exists within the anterior chamber whereby warm AH circulates from the pupil downward adjacent to the air‐cooled cornea and upward near the lens where the temperature is warmer. This thermal circulation is responsible for the deposition of cellular material – termed keratic precipitates – on the inferior aspect of the corneal endothelium.

      Aqueous Humor Formation

      The ciliary body has several critical functions, including production of AH by active secretion, ultrafiltration, and diffusion; generation of IOP through the aqueous dynamic process; influencing through its musculature the conventional (i.e., corneoscleral trabecular meshwork [TM] or pressure‐sensitive) AH outflow; provision of blood and nerve supplies for the anterior segment; control of accommodation via its musculature; formation of the BAB; and provision of the entry for nonconventional (i.e., uveoscleral or pressure‐insensitive) AH outflow. Furthermore, the ciliary body is also rich in antioxidant systems, with significant concentrations of catalase, superoxide dismutase, and glutathione peroxidase types I and II. In addition, the ciliary body is the major drug detoxification center in the eye, with its microsomes containing the cytochrome P450 proteins, which catalyze many drugs.

The bilayered ciliary epithelium, consisting of the outer PE and inner nonpigmented epithelium (NPE), is the site for AH secretion. At their apical borders, the PE and NPE connect via gap junctions to form an intricate network (Figure 2.5). Adjacent NPE cells are joined by tight junctions to form a barrier that inhibits paracellular diffusion.

AH is formed by three basic mechanisms: (i) diffusion, (ii) ultrafiltration, and (iii) active secretion by the NPE. The processes of diffusion and ultrafiltration form the “reservoir” of the plasma ultrafiltrate in the stroma of the ciliary body, from which the AH is derived via active secretion by the ciliary epithelium. Energy‐dependent active transport is required to secrete solutes against a concentration gradient across the basolateral membrane of the NPE; it is the most important factor in AH formation. Two enzymes critical in this process, Na⁺–K⁺‐ATPase and carbonic anhydrase (CA), are abundantly present in the NPE. The Na⁺–K⁺‐ATPase is membrane bound and is found in the highest concentrations along the basolateral interdigitation of these cells. Inhibition of the Na⁺–K⁺‐ATPase with cardiac glycosides (e.g., ouabain) or vanadate causes a marked decrease in aqueous formation.

Figure 2.5 Schematic of AH production across the PE and NPE of the ciliary body. Note the position of the critical enzyme Na⁺–K⁺‐ATPase on the basolateral enzyme of the NPE. CA, also critical to AH formation, is abundant in the cytoplasm of both the NPE and PE. Ion transporters and channels facilitate transfer of Na⁺, K⁺, chloride (Cl⁻) and bicarbonate (HCO₃ ⁻) into, between, and out of the NPE and PE, while aquaporins enable water movement. Relative solute concentrations that most markedly differ between aqueous humor and plasma can be found at the bottom.

      Due to the primary active secretion of sodium, other molecules and ions cross over the epithelium by secondary active transport. As a consequence, increased concentrations of ascorbate, amino acids, and chloride are observed in AH relative to plasma in most mammalian species. Electroneutrality is maintained by anions accompanying the actively transported sodium; channels allow passage of chloride on the basolateral NPE membrane and a passive transporter exchanges bicarbonate for chloride.

      CA is abundant in the cytoplasm and on the basal and lateral membranes of the NPE and PE and catalyzes the following reaction:

Formation of bicarbonate by CA is essential for secretion of AH, such that inhibition of CA results in decreased active transport of sodium by the NPE; it is unclear how this process occurs, although several hypotheses exist. Topical and systemic CA inhibitors substantially decrease AH production, therefore reducing IOP, and are thus useful in the management of glaucoma in animals and humans.

      Aqueous Humor Composition

As an ultrafiltrate of plasma, the compositions of AH and plasma are similar, with a few notable exceptions: a low protein concentration, high ascorbate and lactate concentrations, and reduced amounts of urea, glucose, and nonprotein nitrogen occur within AH versus plasma (Figure 2.6). Thus, breakdown of the BAB modifies the composition of the AH, primarily by the addition of proteins and prostaglandins, and increases light scattering. The resultant Tyndall effects makes a slit‐lamp beam evident within the anterior chamber, an observation clinically known as “aqueous flare.” With the addition of proteins, the aqueous composition closely approximates that of plasma and is termed plasmoid aqueous. Plasmoid aqueous in domestic animals forms fibrin clots easily due to high concentrations of the glycoprotein fibrinogen. Unless treated pharmacologically, these fibrin clots can cause numerous complications, including anterior and/or posterior synechiae or adhesions between the iris and the cornea and/or lens.

Figure 2.6 AH drainage occurs via the traditional and uveoscleral outflow pathways in the iridocorneal angle of the dog. The ciliary body epithelium produces AH, which flows from the posterior chamber, through the pupil, and into the anterior chamber. Then, AH drains through the pectinate ligament to enter the TM. In the traditional outflow pathway, AH enters the AAP to drain anteriorly to the episcleral and conjunctival veins or posteriorly into the scleral venous plexus (SVP) and vortex veins. With uveoscleral outflow, AH flows through the ciliary muscle interstitium to the supraciliary and suprachoroidal spaces to diffuse out the sclera.

In addition to protein and ascorbate, other organic compounds constitute the AH, and their concentrations vary relative to plasma. In most mammalian species, the concentration of amino acids in the AH is higher than that in the plasma, suggesting that active transport of amino acids is occurring across the ciliary epithelium. In the dog, however, amino acid concentrations are less in AH than in plasma. In this species, the vitreous may act as a “sink” for some of the amino acids, thus causing the deficiency.

      The major cations in the AH are sodium, potassium, calcium, and magnesium, with sodium comprising 95% of the total cation concentration. Sodium enters the AH via active transport, with a net flow of water into the posterior chamber. The major anions in AH are chloride, bicarbonate, phosphate, ascorbate, and lactate. The chloride and bicarbonate ions enter with sodium, but their concentrations vary among species.

      Aqueous Humor Regulation

      The rate of aqueous