Читать книгу Essentials of Veterinary Ophthalmology - Kirk N. Gelatt - Страница 90

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.