Basic Pathogenic Mechanisms Operating in Experimental Models of Acute Anterior Uveitis

Acute anterior uveitis is a recurrent inflammatory disease of the eye that occurs commonly, is distressing for the patient, and may have potentially blinding sequelae. The pathogenesis of the disease is poorly understood, and anti-inflammatory treatment is consequently non-specific and may be associated with significant complications. Animal models are a possible key to a better understanding of this disease. In one model, rats and mice develop a relatively short-lived anterior uveal inflammation almost immediately after systemic injection of bacterial endotoxin. Accumulating evidence suggests that cytokine production by resident uveal macrophages initiates endotoxin-induced uveitis which is characterized by an infiltration of neutrophils and mononuclear cells. A second model displays features in keeping with a delayed-type hypersensitivity immune response. Experimental melanin-induced uveitis is an acute recurrent uveitis with delayed onset but extended duration, observed when rats are immunized with bovine ocular melanin. Both animal models have clinical features in common with acute anterior uveitis, although experimental melanin-induced uveitis appears to mimic the human disease more closely. Novel treatment options to target implicated inflammatory cells and molecules are currently under consideration.