Undifferentiated uveitis (intraocular inflammation, IOI) is an idiopathic sight-threatening, presumed autoimmune disease, accountable for ~ 10% of all blindness in the developed world. We have investigated the association of uveitis with inflammatory bowel disease (IBD) using a mouse model of spontaneous experimental autoimmune uveoretinitis (EAU). Mice expressing the transgene (Tg) hen egg lysozyme (HEL) in the retina crossed with 3A9 mice expressing a transgenic HEL-specific TCR spontaneously develop uveoretinitis at post-partum day (P)20/21. Double transgenic (dTg TCR/HEL) mice also spontaneously develop clinical signs of colitis at ~ P30 with diarrhoea, bowel shortening, oedema and lamina propria (LP) inflammatory cell infiltration. Single (s)Tg TCR (3A9) mice also show increased histological LP cell infiltration but no bowel shortening and diarrhoea. dTg TCR/HEL mice are profoundly lymphopenic at weaning. In addition, dTg TCR/HEL mice contain myeloid cells which express MHC Class II-HEL peptide complexes (MHCII-HEL), not only in the inflamed retina but also in the colon and have the potential for antigen presentation. In this model the lymphopenia and reduction in the absolute Treg numbers in dTg TCR/HEL mice is sufficient to initiate eye disease. We suggest that cell-associated antigen released from the inflamed eye can activate colonic HEL-specific T cells which, in a microbial micro-environment, not only cause colitis but feedback to amplify IOI.
This work was funded by Fight for Sight, The Eye Charity [CSO project grant award: 3031-3032; grant code: RG14602-10], and The Development Trust of the University of Aberdeen (Saving Sight in Grampian) [grant codes: RG-12663, and RG-14251]. We thank the Iain Fraser Flow Cytometry core facility1 and the Microscopy and Histology core facility2 of the University of Aberdeen, and the NHS Grampian Pathology Department3, particularly Andrea Holme1, Ailsa Laird1, Gillian Milne2, Debbie Wilkinson2, Lucy Wight2, Linda Davidson3 and Jacqueline Strachan3. We thank Petruta Morvay (University of Exeter, Exeter, UK) for her valuable assistance with the preparation of bowel Swiss rolls.