1

2

3

4

5

FIGURE 3-20

Layers of Bruch’s membrane, delineated on basis of electron microscope studies: 1, Interrupted basement membrane of choriocapillaris; 2, outer collagenous zone; 3, elastic layer; 4, inner collagenous zone; 5, basement membrane of retinal

pigment epithelial cells. (From Hogan MJ, Alvarado JA, Weddell JE: Histology of the human eye, Philadelphia, 1971, Saunders.)

Clinical Comment: Presbyopia

PRESBYOPIA  is the loss of the ability to accommodate; it a normal age-related change and the subject of continuing research. In rhesus monkeys, the tendon that attaches

the ciliary muscle to the scleral spur shows extensive age-related structural changes: It thickens with age and becomes surrounded by a dense layer of collagen, thus losing its elasticity. This loss of elasticity restricts muscle movement and hampers accommodation.30 A similar mechanism may be one component of human presbyopia; however, other changes are likely involved including changes involving the lens itself (see Chapter 5).

Aqueous Production

The ciliary body capillaries and the ciliary epithelial layers are significant factors in the production and secretion of aqueous. The stroma within the ciliary processes contains a dense network of fenestrated capillaries, and the number and shape of the processes provides a large surface area for secretion into the posterior chamber. Three mechanisms contribute to production and secretion: diffusion, ultrafiltration, and active secretion.31 Diffusion occurs when an uneven distribution of molecules exists across a membrane and the molecules

move from the higher concentration to the lower concentration. Ultrafiltration occurs as bulk flow across a semipermeable membrane augmented by a hydrostatic pressure. In active secretion molecules are transported across the membrane against a concentration gradient in an energy-utilizing process; active secretion likely accounts for 80% to 90% of aqueous production.15

Pressure on the ciliary stroma side of the two-layered epithelia is estimated at greater than 15 mm Hg, providing a driving force that moves solution minus macromolecules across the zonula occludens barrier of the nonpigmented epithelium, thus producing an ionic concentration comparable to blood plasma. An oncotic gradient of approximately 14 mm Hg could move water across the semipermeable membrane of the nonpigmented epithelium from a solution with low concentration of macromolecules (the aqueous) into a higher concentration of macromolecules (blood plasma), counteracting the ultrafiltration process. As these forces are in the opposite direction, it is unclear how great a factor ultrafiltration actually is in aqueous production because it might be offset by water movement back into the ciliary processes.23

As molecules exit the blood through the walls of the ciliary capillaries, they move through the stroma and the epithelia. The model of ion movement through these cells is still theoretical; transport mechanisms have been identified but the regulation of those mechanisms is not clear.23,31-33 The two layers of epithelium are thought to function together as a syncytium due to the extensive gap junctions joining the cells within each layer as well those between the two layers.

The driving force for secretion of the fluid is produced by transepithelial ionic transport across this bilayered ciliary epithelium.34 Ions enter the basolateral pigmented ciliary epithelium (PE); (Na+ and Cl− likely enter by Na+/H+and Cl−/HCO3− exchangers and the Na+/K+/2Cl− cotransporter), then diffuse through the apical membrane into the extracellular fluid, as well as directly into the nonpigmented ciliary epithelium (NPE) through gap junctions.23,34 The active ATPase pump within the NPE cell accounts for a relatively low concentration of Na+ in the NPE, creating a driving force for Na+ movement. The Na+/H+ exchange and the Na+/K+/2Cl− transporter maintain the cycle of Na+ passage.

Ions exit the basolateral membrane of the NPE through ionic pumps, ion channels, and cotransporters into the posterior chamber; the electrical voltage change due to movement of ions can drive increased movement of Na+ and Cl− and thus shift water. Potassium ions that were brought into the cell by Na+/K+ ATPase pumps are kept circulating by K+ channels in the basolateral membrane.34 The coordination of ion pumps, channels, and cotransporters in these two epithelia, as well as aquaporins in the NPE that facilitate water movement, produce the substance secreted into the posterior chamber as