Understanding trabecular meshwork physiology: a key to the control of intraocular pressure?

he anterior and posterior chambers of the eye are filled with aqueous humor, a fluid with an ionic composition very similar to the blood plasma and with two main functions: to supply nutrients to the avascular structures of the eye, cornea, and lens and to maintain intraocular pressure (IOP) within its physiological range, because it is the volume of aqueous humor in the eye chambers that determines the IOP value. Both nutrition of lenses and maintenance of IOP are critical for a normal visual process. Aqueous humor undergoes a constant turnover. Initially, aqueous humor is secreted to the posterior chamber of the eye by the ciliary processes of the ciliary body in a process known as aqueous humor inflow. The mechanisms of aqueous humor inflow have been well documented and combine ultrafiltra-tion from arterial blood and active secretion. Aqueous humor then reaches the anterior chamber by crossing the pupil and exchanges its contents with cornea and lens. Finally, aqueous humor is recycled by exiting the eye and returning to systemic circulation in a process defined as aqueous humor outflow (Fig. 1). Outflow rate is then one of the two elements of the equation defining aqueous humor volume and, thereby, IOP value. There are two different pathways of aqueous humor out-flow, both located in the iridocorneal angle of the eye (Fig. 1). The uveoscleral or nonconventional pathway refers to the aqueous humor leaving the anterior chamber by diffusion through intercellular spaces among ciliary muscle fibers [reviewed by Bill (2)]. Although this seems to be a minority outflow pathway in humans, the uveoscleral or nonconven-tional pathway is the target of specific antiglaucoma drugs (latanoprost, a prostaglandin F 2D analog) that increase the functionality of this route. In the human eye, the main outflow route is the trabecular or conventional outflow pathway. On this route, aqueous humor exits the eye through a well-struc-tured tissue called the trabecular meshwork (TM). After crossing the TM, aqueous humor reaches Schlemm's canal (Fig. 1), which drains directly to the aqueous veins. Aqueous humor outflow via the trabecular pathway is IOP dependent, usually measured as outflow facility, and expressed in microliters per minute per millimeter of mercury. Among glaucomas, most of those known as open-angle glaucomas (|85% of total glaucomas) are caused by an increase in the resistance to aqueous humor drainage through the TM and/or Schlemm's canal. Sequentially, first the outflow facility decreases and then, as a …