title: Transgenic Expression of IFN-gamma in the Eye as a Model for Studying Ocular Inflammatory Disease
abstract: To study the effects of IFN-gamma on intraocular inflammation we used mice with transgenic expression of IFN-gamma in the retina of the eye. These transgenic mice (rhogamma) were challenged intraocularly with soluble and cellular antigens and then studied for development of uveitis and delayed-type hypersensitivity reaction after a second intracutaneous challenge with the same antigen. Further experiments tested the influence of IFN-gamma on infection with herpes simplex (HSV) by intraocular virus inoculation in rhogamma mice and rhogamma mice crossed with MHC class I or class II deficient mice. Pathology was studied by morphology immunocytochemistry and electron microscopy. Growth of HSV was assessed by plaque assay on Vero cells. Rhogamma transgenic mice produced IFN-gamma in the photoreceptors of the retina and secreted the cytokine into the vitreous of the eye. These animals suffered from cellular infiltration of the eyes, cataracts, and degeneration of the photoreceptors. In contrast to control mice, transgenic mice had increased uveal inflammation and developed delayed-type hypersensitivity after intraocular challenge with alloantigens such as allogeneic splenocytes and inactivated virus. Rhogamma mice also experienced protection from infection with herpes simplex virus-1 (HSV-1) and HSV-2, suffering a less severe course of disease than control mice. Cytokine-induced protection was not based on viral replication block and did not require simultaneous expression of MHC class I and class II. The rhogamma transgenic mouse provided a model suitable for testing mechanisms of IFN-gamma action in the eye in vivo. The surprising results offer new arguments in the evaluation of cytokine effects.
authors.affiliation: Edinger-Institut, Universitat Frankfurt, Frankfurt, D-60528, Germany
authors.initials: KD
authors.lastname: Geiger
authors.initials: NE
authors.lastname: Sarvetnick