Interphotoreceptor retinoid binding protein peptide-induced uveitis in B10.RIII mice: characterization of disease parameters and immunomodulation.
Experimental autoimmune uveoretinitis (EAU) can be induced in the B10.RIII mice following immunization with bovine interphotoreceptor retinoid binding protein (IRBP) and human IRBP(161--180)peptide. This study examines the value of the human IRBP(161--180)peptide model in the B10.RIII mice, as a suitable model of EAU in order to examine immunotherapies. Having established a reliable and consistent immunization protocol of 25 micro g peptide and no PTX, the time course of histopathology was performed, which graded both cellular and structural scores individually. Disease was typically of an acute nature, characterized by rapid onset of a massive inflammatory response, resulting in extensive damage to the rod outer segments (ROS) and neuronal layers. Treatment with potent immunosuppressive agents, CD4-specific monoclonal antibodies resulted in the inhibition of disease and a reduction in disease incidence. Treatment with p55-tumor necrosis factor receptor-Ig (p55-TNFR-Ig) fusion protein reduced structural damage to the retina despite a high level of cellular infiltration in the eye, suggesting that target organ damage in an acute model of EAU can be modulated.
Hankey
D J
DJ
Department of Clinical Ophthalmology, Institute of Ophthalmology, University College London, London, UK. dhankey@hgmp.mrc.ac.uk
Lightman
S L
SL
Baker
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D007167:Immunotherapy; D051379:Mice; D018168:Receptors, Retinoic Acid / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D015866:Uveitis, Posterior / Q000276:immunology* / Q000628:therapy
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D018168:Receptors, Retinoic Acid; D018124:Receptors, Tumor Necrosis Factor