Effect of Interferon Gamma on the Onset and Severity of Uveitis

Egwuagu, Charles

Abstract

Interferon-g (IFNg) is a pleiotropic cytokine that has been implicated in immunopathogenic mechanisms of a number of inflammatory diseases of autoimmune or infectious disease etiology. However, its exact role is still a matter of debate. In experimental mouse models, IFNg has been shown to exacerbate autoimmune thyroiditis, insulin-dependent diabetes mellitus and autoimmune neuritis while it confers protection against experimental allergic encephalomyelitis and experimental uveitis. In this study, we used transgenic rats with constitutive expression of IFNg in the eye to study its paracrine effects and to investigate whether local production of IFNg also confers protection against uveitis in the rat species. In this study, we show that chronic exposure of ocular cells to IFNg results in activation of pro-inflammatory genes, the development of chronic choroiditis, formation of retinal in-foldings, progressive degeneration of the neuroretina and the selective loss of ganglion cells by apoptosis. Some of these effects are key features of glaucoma and nutritional amblyopia In contrast to its protective systemic effect in the mouse, constitutive secretion of IFNg in the rat eye was found to predispose to development of severe anterior and posterior uveitis and induction of retinal degenerative processes that impair visual acuity. These results suggest that our TR rats constitute an important model for the study of etiologic mechanisms of glaucoma and uveitis. - Retinal degeneration; apoptosis; transgenic rat; uveitis; interferon-gamma