Abstract
Animal models of autoimmunity to the retina mimic specific features of human uveitis, but no model by itself reproduces the full spectrum of human disease. We compared three mouse models of uveitis that target the interphotoreceptor retinoid binding protein (IRBP): (i) the “classical” model of experimental autoimmune uveitis (EAU) induced by immunization with IRBP; (ii) spontaneous uveitis in IRBP T cell receptor transgenic mice (R161H) and (iii) spontaneous uveitis in Autoimmune Regulator (AIRE)−/− mice. Disease course and severity, pathology and changes in visual function were studied using fundus imaging and histological examinations, optical coherence tomography and electroretinography. All models were on the B10.RIII background. Unlike previously reported, IRBP-induced EAU in B10.RIII mice exhibited two distinct patterns of disease depending on clinical scores developed after onset: severe monophasic with extensive destruction of the retina and rapid loss of visual signal, or lower grade with a prolonged chronic phase culminating after several months in retinal degeneration and loss of vision. R161H and AIRE−/− mice spontaneously developed chronic progressive inflammation; visual function declined gradually as retinal degeneration developed. Spontaneous uveitis in R161H mice was characterized by persistent cellular infiltrates and lymphoid aggregation, whereas AIRE−/− mice characteristically developed multi-focal infiltrates and severe choroidal inflammation. These data demonstrate variability and unique distinguishing features in the different models of uveitis, suggesting that each one can represent distinct aspects of uveitis in humans.
Highlights
Non-infectious uveitis involves a range of clinical pathologies including iritis, cyclitis, choroiditis, retinitis, and uveoretinitis, and is estimated to underlie 10–15% of blindness in the Western world [1,2]
experimental autoimmune uveitis/uveoretinitis (EAU) can be induced in mice [6] and in rats [7,8,9] by active immunization with retinal antigens that are recognized by lymphocytes of uveitis patients, such as interphotoreceptor retinoid-binding protein (IRBP) and retinal soluble antigen (S-Ag)
Disease severity and course were evaluated and compared between three models of uveitis, the ‘‘classical’’ immunization-induced EAU model, spontaneous uveitis developing in R161H IRBP T cell receptor (TCR) transgenic mice, and spontaneous uveitis developing in AIRE2/2 mice (Figure 2)
Summary
Non-infectious uveitis involves a range of clinical pathologies including iritis, cyclitis, choroiditis, retinitis (including retinal vasculitis), and uveoretinitis, and is estimated to underlie 10–15% of blindness in the Western world [1,2]. Due to practical and ethical limitations of human studies, the animal model of experimental autoimmune uveitis/uveoretinitis (EAU) [4,5] has been used to study the basic mechanisms of disease. The main features of EAU in animals are retinal and/or choroidal inflammation, retinal vasculitis, photoreceptor destruction and loss of visional function [10]. As such they reproduce many essential clinico-pathological features of human uveitis [11]
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