NASAL ADMINISTRATION OF RETINAL ANTIGENS MAINTAINS IMMUNOSUPPRESSION OF UVEORETINITIS IN CYCLOSPORINE-A-TREATED LEWIS RATS - FUTURE TREATMENT OF ENDOGENOUS POSTERIOR UVEORETINITIS

Purpose: Current treatment of autoimmune endogenous posterior uveoreti nitis (EPU) is limited by drug toxicity, unpredictable relapses on dos e reduction and resistance to therapy, Administration of autoantigens via gastrointestinal or respiratory mucosa prior to antigen exposure i nduces immune hyporesponsiveness (mucosal tolerance) to further antige n sensitisation, In this study we assessed whether mucosal tolerance i nduction was possible after immunisation with retinal antigens in expe rimental autoimmune uveoretinitis (EAU) in animals that were short-ter m immunosuppressed with cyclosporin A (CsA) to determine whether mucos al administration of retinal antigens can maintain immunosuppression i n sensitised and immunosuppressed individuals. Methods: Female Lewis r ats were immunised with retinal extract (RE) and then treated as follo ws, Group 1 received no specific therapy and served as control; group 2 were fed CsA from day 7 to day 20 postimmunisation; group 3 received inhalational tolerance therapy with RE in addition to CsA; tolerance therapy was continued after day 20 when CsA was stopped, Experiments v arying the timing and dosage of both tolerising and immunising antigen were also performed, the details of which are described. Incidence, d ay of onset and clinical activity were recorded and histopathological assessment of intraocular inflammation, in particular the extent of au toimmune target-organ damage, was graded semiquantitatively. Results: Compared with controls and group 2, group 3 showed both a marked delay in disease onset and a reduction in disease severity, This effect was both dose and dose-timing dependent, Tissue damage assessed in terms of preservation of rod outer segments was significantly less in group 3. Conclusions: The success of combination therapy, clinically, remain s unknown at present but these results support continuing present clin ical trials of mucosal tolerance therapy and in particular have future implications for either maintaining or inducing immunosuppression in autoimmune diseases in combination with present immunosuppressive ther apies.