TRANSGENIC MICE EXPRESSING IFN-GAMMA IN THE RETINA DEVELOP INFLAMMATION OF THE EYE AND PHOTORECEPTOR LOSS

Purpose. Inflammatory mediators such as interferon-gamma (IFN-gamma) a re thought to play a role in ocular disease. Although IFN-gamma was fo und in the vitreous of mice with experimentally induced autoimmune uve itis, intracameral injection of this cytokine did not induce intraocul ar inflammation in mice. Therefore, the authors created a transgenic m ouse line using the rhodopsin promoter to direct the expression of IFN -gamma in the photoreceptor cells of the retina. These mice, designate d rho gamma, enabled them to model intraocular inflammatory disease. M ethods. The authors fused a 2.1 kb 5' Hind III fragment from the murin e rhodopsin gene to the IFN-gamma gene and introduced the DNA construc t into fertilized zygotes. These were implanted into pseudopregnant C5 7BL/6 mice, and the resulting progeny were crossed back to balb/c mice . The transgene was identified by Southern blot hybridization. Eyes fr om the rho gamma mice were either fixed in zinc formalin and stained w ith hematoxylin and eosin or were frozen in OCT compound and processed for immunostaining using the indirect immunoperoxidase method with DA B as a chromogen. Results. The rho gamma transgenic mice developed int raocular disease, manifested as intraocular cellular infiltration, los s of photoreceptors, corneal clouding, cataract formation, and epithel ial and microglial proliferation. Additionally, rho gamma mice exhibit ed antigenic changes, comprising GFAP expression on Muller cells, accu mulation of neurofilament on photoreceptors, and expression of MHC cla ss I and class II molecules on retinal cells. Conclusions. IFN-gamma a lters the antigenic properties of intraocular tissue and induces intra ocular inflammation in mice. The results suggest a key position of IFN -gamma in the development of pathologic conditions related to intraocu lar inflammation and provide a useful animal model for the further stu dy of inflammatory disorders, including autoimmune diseases.