TRANSGENIC EXPRESSION OF IFN-GAMMA IN THE MURINE LENS RESULTS IN MULTIPLE OCULAR ABNORMALITIES AND AN EARLY BUT SELF-LIMITED INFLAMMATORY RESPONSE

The anterior chamber of the eye is known to be an immune privileged si te, due to both local and systemic effects on the immune response. Inj ection of IFN-gamma into the anterior chamber (AC) overcomes the suppr ession of antigen-specific delayed hypersensitivity responses normally seen in the eye. Transgenic mice expressing increased IFN-gamma in th e lens under the alpha A-crystallin promoter were produced to determin e whether the proinflammatory effects of IFN-gamma would abolish immun e privilege and promote loss of tolerance as has been seen in non-immu ne privileged tissues. Two alpha C/IFN-gamma transgenic lines are desc ribed which demonstrate multiple ocular and lenticular abnormalities s ome of which are developmental in origin and others that may be second ary to the inflammatory effects of IFN-gamma. A significant inflammato ry cell infiltrate which is observed in the AC and vitreous from birth to 4 weeks of age, consists initially of macrophage and polymorphonuc lear leukocytes and then CD4+ T lymphocytes. However, the infiltrate i s essentially resolved by 6 weeks of age. Therefore, although lens-spe cific expression of IFN-gamma results in early loss of immune privileg e, chronic uveitis does not occur probably due to the lack of continue d IFN-gamma expression.