Visual function in retina-specific TCR-transgenic mice with spontaneous autoimmune uveitis

Abstract

Abstract Autoimmune uveitis is a potentially blinding disease caused by circulating retina-specific T cells. To understand the mechanisms behind autoimmune uveitis, R161 transgenic mice expressing a TCR specific for IRBP, the retinal target protein for autoimmune uveitis in the mouse model, were generated. Three lines of R161 mice expressing the same TCR at different copy numbers have been established: R161H>R161M>R161L. The H and M lines developed spontaneous uveitis with 100% incidence by 2–3 months, whereas the L line developed disease only upon immune perturbation. The expression levels of the R161 TCR transgene correlated with frequency of IRBP-specific CD4 T cells in the peripheral repertoire, and with severity of disease. To study the association of visual function with pathology of uveitis, we examined visual function of R161 lines and compared with their parental strain B10.RIII (WT) by electroretinography (ERG), which measures electrical responses of retinal cells under dark- and light-adapted conditions. Uveitis was monitored and scored weekly by fundoscopy and ERG was performed in the next day following dark adaptation. Overall, as inflammatory scores increased, ERG responses decreased. R161L mice, which develop little or no disease, had visual function equivalent to WT mice. At 16 weeks old when disease in the H and M lines had reached its peak, R161H mice exhibited no and most of R161M mice exhibited poor visual function, whereas only minor reduction of ERG, which is normally observed with age, was detected in R161L and WT mice. The ERG data illustrate an association of visual function with uveitis scores among R161 lines, each of which may serve as a unique model of uveitis with different severity and visual loss.