Abstract
Purpose: :
Experimental autoimmune uveoretinitis (EAU) is an animal model for human non-infectious autoimmune uveitis that displays many pathological features of the human disease. The normal healthy retina contains very few leucocytes, which allows the quantification of changes in cell content with a high degree of sensitivity. Understanding how immunosurveillance of the retina is modified throughout the course of EAU is critical to developing effective therapy for human uveitis. In EAU, following a clinically silent prodromal phase, the first peak of disease is characterised by the accumulation of large numbers of retinal leucocytes. The purpose of this work was to characterise immunosurveillance in the prodrome in response to target organ specific and non-specific cues, to determine whether there were differences in cellular trafficking when this ultimately resulted in disease progression.
Methods: :
EAU was induced in female B10.RIII or C57BL/6 mice by immunisation with retinal autoantigen (retinol binding protein-3 RBP-3, previously known as IRBP) or with an irrelevant foreign peptide (ovalbumin 323-339) in combination with complete Freund’s adjuvant and pertussis toxin. Clinical disease and cellular infiltrate were assessed by topical endoscopic fundus imaging (TEFI) and mulitparameter flow cytometry.
Results: :
At day 5 post immunisation, we detected a significant increase in the number of CD4 positive T lymphocytes and Ly6G positive leukocytes within the ocular tissue in response to immunisation with RBP-3 or ovalbumin. The eye remained clinically normal at this time. Non-specific increases in cell content were still detectable at day 10 and then declined. In the RBP-3 immunised animals, a retinal population of CD4 positive cells was retained and later increased at the peak of clinical disease. Some mice exhibited temporal variation in the initiation of peak disease, indicating that changes in immunosurveillance may be target organ specific.
Conclusions: :
We conclude that immunosurveillance of the immune privileged retina is upregulated in response to both specific and non-specific cues and that the addition of an antigen specific signal poises the retina with a retained population of antigen specific cells, primed to initiate peak clinical disease.
Keywords: autoimmune disease • uveitis-clinical/animal model