thromboxane-a2 and Uveitis

Since prostaglandins (PGs) were originally discovered in the eye in a search for the mediators of the ocular irritative responses, it is not surprising that the first decade of research on the ocular effects of these autacoids concentrated on their potential role in inflammation and other pathological processes. It is clear that PGs, like most other biologically active compounds, can have pathological effects when introduced into the eye in sufficiently high doses. More recent studies indicate, however, that PGs are also involved in the normal physiological processes of the eye, and that some PGs effectively reduce intraocular pressure and may actually moderate rather than mediate ocular inflammation. We must therefore consider the eicosanoids as a new class of potential ocular therapeutic agents. This paper reviews the evidence that these autacoids are actively transported by some tissues, including the ciliary epithelium, and considers the role of such transport processes in the ocular and systemic pharmacokinetics of endogenous eicosanoids and their therapeutically applied prodrugs.

Topics: Animals; Aqueous Humor; Biological Transport, Active; Cats; Cell Membrane Permeability; Ciliary Body; Epithelium; Eye; Female; Glaucoma; Intraocular Pressure; Kinetics; Macular Edema; Prostaglandins; Rabbits; Retinal Vessels; Thromboxane A2; Thromboxane B2; Uveitis

Uveitis comprises a complex group of diseases in which morbidity may depend on the nature of the initial inflammation as well as on the genetic, hormonal, and emotional background of the patient. Uveitis is initiated in every instance by some form of tissue injury. This may occur as an attack on individual cells by organisms such as Toxoplasma gondii or Herpesvirus hominis. Autoimmune disease may be produced as a late result of microbe-induced injury. The development of specific forms of autoimmunity seems to be dependent upon genetic as well as hormonal factors, particularly estrogens. Tissue injury of immunologic origin takes several forms, such as cytotoxic damage from sensitized lymphocytes, immune complex-mediated injury, and injury from the oxidative products of inflammatory cells. In some cases, permanent alteration of uveal vascular permeability results. Recurrent uveitis may be attributed in some instances to the reappearance of infectious organisms in the target tissue. In other cases, recurrence of inflammation may be attributed to the localization of immune complexes in the uveal tract. Changes in immunoregulation can be attributed to pregnancy, aging, and emotional factors. Neurohumoral pathways related to stress-mediated changes in immunoregulation have recently been described in laboratory animals. These pathways may be linked with stress-related recurrences of uveitis in humans.

Topics: Aged; Aging; Antigen-Antibody Complex; Capillary Permeability; Eye Injuries; Female; HLA Antigens; Humans; Keratitis, Dendritic; Neurotransmitter Agents; Pregnancy; Pregnancy Complications, Infectious; Recurrence; SRS-A; Stress, Psychological; Thromboxane A2; Toxoplasmosis, Ocular; Uveitis

Systemic injection of bacterial endotoxin (Lipopolysaccharide, LPS) in experimental animals induces anterior uveitis without major pathological changes in other organs. The present study investigates the effect of LPS on production of inflammatory mediators in cultured bovine pigmented ciliary epithelial cells (CB-cells) by means of radioimmunoassays and bioassays. LPS was found to stimulate CB-cells to secrete prostaglandin E2 and prostacyclin (assayed as its stable metabolite 6-keto-prostaglandin F1a), but not leukotriene B4 or thromboxane A2 (assayed as its stable metabolite thromboxane B2). CB-cells produced membrane-associated interleukin 1-activity in response to LPS, but no tumor necrosis factor-activity was found after challenge of CB-cells with LPS. The direct effect of LPS on production of inflammatory mediators by cells from the anterior uvea could play a role in the pathophysiology of endotoxin-induced uveitis.

Topics: Animals; Cattle; Cells, Cultured; Ciliary Body; Dinoprostone; Epithelium; Epoprostenol; Inflammation; Interleukin-1; Leukotriene B4; Lipopolysaccharides; Radioimmunoassay; Thromboxane A2; Tumor Necrosis Factor-alpha; Uveitis