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Jun Chen, Haohua Qian, Chi-Chao Chan, Rachel R Caspi; Clinical and functional evaluation of experimental autoimmune uveitis in B10.RIII mice: monophasic versus biphasic forms. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5305.
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Non-infectious uveitis in humans is an autoimmune disease of the retina and uvea that leads to blindness. Its laboratory equivalent is experimental autoimmune uveitis (EAU) induced in susceptible rodents by immunization with retinal antigens. The murine model of EAU has been particularly useful, permitting to dissect basic mechanisms as well as serving as a template for translational therapies. The B10.RIII mouse strain is the most susceptible strain known. To characterize EAU in the B10.RIII strain, we used multiple methodologies including non-invasive assessments in comparison with histology for disease evaluation.
EAU was induced in B10.RIII mice by immunization with IRBP161-180 in the absence of pertussis toxin. Disease was evaluated longitudinally using non-invasive clinical assessments by fundus examination and photography, optical coherence tomography and functional evaluation by electroretinography (ERG), which were then compared to histopathology.
The EAU model in the B10.RIII strain had been thought until now to only manifest an acute-monophasic pattern of disease. Unlike previously reported, we found that IRBP-immunized EAU in B10.RIII mice exhibited two distinct patterns of disease depending on clinical scores developed after onset: (i) severe monophasic form of EAU with diffuse/extensive destruction of the retina, followed by a rapid retinal atrophy and loss of visual signal two weeks post immunization, or (ii) lower grade of EAU with an initial acute phase, followed by a prolonged chronic phase and partial recovery of the ERG response, culminating in focal retinal degeneration and loss of vision after 6-7 months.
We demonstrate for the first time that EAU model in the B10.RIII strain can be either monophasic or biphasic, with distinguishing features. These findings can affect the choice of animal model of human uveitis as a platform to evaluate effects of investigational therapeutic modalities.
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