Ciliary body control of organic anions in the aqueous humor of the eye

Aqueous humor is the transparent fluid surrounding the lens that helps maintain the shape and optical properties of the eye. Aqueous humor is produced by the ciliary body epithelium, a sheet of cells that separates the bloodstream from the aqueous compartment. The concentration of a number of organic anions, such as uric acid, is lower in aqueous humor than plasma, suggesting that they are actively removed. Organic anions represent a relatively broad class of chemicals, including hormones, metabolic intermediates, drugs and environmental contaminants, which in excess can disrupt normal biological processes. The ability to control aqueous humor concentrations of organic anions is of particular importance to the lens, as this tissue has no blood supply. The ciliary body epithelium, being in contact with both the blood supply and aqueous humor, is uniquely positioned to regulate the chemical composition of the aqueous humor. Given that organic anions are relatively impermeable to plasma membranes their efficient movement across ciliary body epithelial cells requires facilitation by membrane transport proteins (organic anion transporters) as well as the input of cellular energy. The aims of this proposal are: 1) to show that the ciliary body epithelium is capable of transporting organic anions in the aqueous humor-to-blood direction and to define the energetic requirements; 2) to determine which organic anion transporters are present in the ciliary body epithelium and where they are expressed; and 3) to identify which of the organic anion transporters are involved in the transport process by specifically inhibiting them. The aims outlined in this proposal support the long-term objective of this research program, which is to understand the processes that regulate the chemical composition of the aqueous humor, a saline vital for vision.