Aqueous Humor Production

As shown in Figure 1-2 in Chapter 1, aqueous humor is produced by the ciliary processes in the posterior chamber and flows through the pupil into the anterior chamber. The average rate of aqueous humor production is 2–3 μL/min while awake, decreasing by about 50% during sleep. Because the anterior segment volume is approximately 200–300 μL, the eye’s total volume of aqueous humor is turned over about every 100 minutes. The ciliary body contains approximately 80 ciliary processes, each of which is composed of a double layer of epithelium over a core of stroma and a rich supply of fenestrated capillaries (Fig 1-2). These capillaries are supplied mainly by branches of the major arterial circle of the iris. The apical surfaces of both the outer pigmented and the inner nonpigmented layers of epithelium face each other and are joined by tight junctions, which are an important component of the blood–aqueous barrier. The inner nonpigmented epithelial cells, which protrude into the posterior chamber, contain numerous mitochondria and microvilli; these cells are thought to be the site of aqueous production. The ciliary processes provide a large surface area for secretion.

Figure 2-1 Anatomic details of the anterior chamber angle and ciliary body. A, The 2 layers of the ciliary epithelium, showing apical surfaces in apposition to each other. Basement membrane (BM) lines the double layer and constitutes the internal limiting membrane (ILM) on the inner surface. The nonpigmented epithelium is characterized by large numbers of mitochondria (M), zonula occludens (ZO), and lateral and surface interdigitations (I). The pigmented epithelium contains numerous melanin granules (MG). Additional intercellular junctions include desmosomes (D) and gap junctions (GJ). B, Light micrograph of the anterior chamber angle shows the Schlemm canal (black arrow), adjacent to the trabecular meshwork in the sclera. One of the external collector vessels can be seen (red arrow) adjacent to the Schlemm canal. C, Pars plicata of the ciliary body showing the 2 epithelial layers in the eye of an older person. The nonpigmented epithelial cells measure approximately 20 μm high by 12 μm wide. The cuboidal pigmented epithelial cells are approximately 10 μm high. The thickened ILM (a) is laminated and vesicular; such thickened membranes are characteristic of older eyes. The cytoplasm of the nonpigmented epithelium is characterized by its numerous mitochondria (b) and the cisternae of the rough-surfaced endoplasmic reticulum (c). A poorly developed Golgi apparatus (d) and several lysosomes and residual bodies (e) are shown. The pigmented epithelium contains many melanin granules, measuring about 1 μm in diameter, located mainly in the apical portion. The basal surface is irregular, with many fingerlike processes (f). The basement membrane of the pigmented epithelium (g) and a smooth granular material containing vesicles (h) and coarse granular particles are seen at the bottom of the figure. The appearance of the basement membrane is typical of older eyes and can be discerned with the light microscope (×5700).

(Part A reproduced with permission from Shields MB. Textbook of Glaucoma. 3rd ed. Williams & Wilkins; 1992. Part B courtesy of Nasreen A. Syed, MD. Part C modified with permission from Hogan MJ, Alvarado JA, Weddell JE. Histology of the Human Eye. Saunders; 1971:283.)

Aqueous humor enters the posterior chamber by the following physiologic mechanisms:

• active secretion, which takes place in the double-layered ciliary epithelium

• ultrafiltration

• simple diffusion

Active secretion refers to transport that requires energy to move sodium, chloride, bicarbonate, and other ions (currently unknown) against an electrochemical gradient. Active secretion is independent of pressure and accounts for the majority of aqueous humor production. It involves, at least in part, activity of the enzyme carbonic anhydrase II. Ultrafiltration refers to a pressure-dependent movement along a pressure gradient. In the ciliary processes, the hydrostatic pressure difference between capillary pressure and IOP favors fluid movement into the eye, whereas the oncotic gradient between the two resists fluid movement. The relationship between secretion and ultrafiltration is not known. Diffusion involves the passive movement of ions, based on charge and concentration, across a membrane.

In humans, aqueous humor has a higher concentration of hydrogen and chloride ions, a higher concentration of ascorbate, and a lower concentration of bicarbonate compared with plasma. In the normal eye, the blood–aqueous barrier keeps the aqueous humor essentially protein-free (1/200–1/500 of the protein found in plasma), allowing for optical clarity. Albumin accounts for approximately half of the total protein. Other components of aqueous humor include growth factors; several enzymes such as carbonic anhydrase, lysozyme, diamine oxidase, plasminogen activator, dopamine β-hydroxylase, and phospholipase A2; and prostaglandins, cyclic adenosine monophosphate (cAMP), catecholamines, steroid hormones, and hyaluronic acid. The composition of the aqueous humor is altered as it flows from the posterior chamber, through the pupil, and into the anterior chamber. This alteration occurs across the hyaloid face of the vitreous, the surface of the lens, the blood vessels of the iris, and the corneal endothelium; and it is secondary to other dilutional exchanges and active processes. See BCSC Section 2, Fundamentals and Principles of Ophthalmology, for further discussion of aqueous humor composition and production.

Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.