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Pathophysiology

Animal models of uveitis

Experimental models of uveitis have contributed greatly to our understanding of uveitis. Each of these models involves the activation of the immune system against specific retinal or uveal tract antigens (Box 79.2).[7] During induction of experimental autoimmune uveitis or uveoretinitis (EAU), animals are sensitized to known retinal antigens such as retinal S-antigen, RPE65,[8] or interphotoreceptor-binding protein (IRBP),[9,10] which are emulsified in complete Freund's adjuvant to augment the immune response. A second agent such as pertussis toxin is also used to activate the immune response further. Using this technique, inflammation of the iris, ciliary body, retina, and choroid is consistently observed. With this reproducible technique, it is possible to study the cellular components, soluble mediators and their receptors, therapies, and drug delivery systems targeted against the inflammatory response.[11]

Box 79.2 

Cellular and soluble mediators of inflammation in uveitis

      Animal models of uveitis, particularly experimental autoimmune uveitis, have been important in characterizing the pathogenesis of uveitis, as well as in studying immunosuppressive agents for the treatment of disease
      The relationship between immunogenetics and the clinical expression of uveitis remains under investigation; however, the recent identification of the NOD2 gene mutation in patients with ocular and systemic granulomatous inflammation is supportive of the importance of genetics in uveitis
      Immune cells implicated in uveitis include CD4+ T-helper cells, cytotoxic CD8+ T cells, B cells, macrophages, and natural killer cells
      Subtypes of CD4+ T-helper cells include Th1 and Th17 cells, which are thought to be proinflammatory. Other CD4+ T-helper cell subtypes may play an immunoregulatory role
      Interleukin-1, interleukin-6, and tumor necrosis factor-α are key proinflammatory cytokines seen in uveitis
      Mechanisms of immunoregulation include peripheral tolerance (active suppression and immune ignorance) and central tolerance (thymic-negative selection). Loss of these control mechanisms may be relevant to the clinical expression of uveitis

Endotoxin-induced uveitis (EIU) has also been …