Aims-Administration of unfractionated retinal antigen(s) (retinal extract, RE) suppresses RE induced experimental autoimmune uveoretinitis (EAU) and oVers a potential therapeutic alternative to nonspecific immunosuppressive therapies for posterior uveitis and autoimmune diseases. S-Ag and interphotoreceptor retinoid binding protein (IRBP) are two major autoantigens within soluble RE. It was aimed to assess, firstly, as has previously been shown with S-Ag, if IRBP can induce intranasal tolerance and, secondly, the contribution of both these major autoantigens to tolerance induction by whole RE. Methods-Animals were tolerised by intranasal administration with S-Ag or IRBP, either alone or in combination, or RE before immunisation with either IRBP or RE. Control animals were administered nasally either PBS or MBP. Daily clinical responses were recorded biomicroscopically and histological grades were obtained using a semiquantitative scoring system. Weekly serum antibody levels to retinal antigens were measured by ELISA and delayed hypersensitivity responses (DTH) were assessed by skin reactivity to intradermal inoculation with retinal or non-specific antigens. Results-Microgram doses of IRBP successfully suppressed both clinically and histologically IRBP induced EAU. This suppression was accompanied by reduced antigen specific DTH reactivity but maintained T cell dependent (IgG2a) antibody responses. Furthermore, combined S-Ag and IRBP administration aVorded equal suppression of RE induced EAU when compared with RE therapy alone. Suppression of RE induced EAU was not achieved with administration of a nonretinal specific autoantigen, MBP. Although individually, both S-Ag and IRBP suppressed RE induced EAU, whole RE was unable to protect against IRBP induced disease. Conclusions-Intranasal administration of IRBP suppressed IRBP induced EAU in the Lewis rat. S-Ag and IRBP are the major contributors to the tolerogenicity within RE, despite the known uveogenicity of other retinal antigens within RE and induction of tolerance was retinal antigen specific. Furthermore, suppression induced by single antigen administration is antigen specific although concomitant bystander suppression may also play a role. RE was unable to protect against IRBP induced disease despite tolerogenic levels of antigen within RE. Although this may be due in part to a dose eVect of either tolerising or immunising antigen, further investigation into the possible antigen dominance of IRBP or mucosal processing of combinations of antigens is necessary so that the full eYcacy of mucosal tolerance therapy can be assessed. (Br J Ophthalmol 1997;81:61-67)

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Background/aim-Nasal administration of retinal antigens induces systemic tolerance which results in suppression of experimental autoimmune uveoretinitis (EAU) when subsequently exposed to antigen. The aim was to establish if tolerance induction alters retinal infiltrating leucocyte phenotype and cytokine profile in tolerised animals when there is significantly reduced tissue destruction despite immunisation with retinal antigen. Conclusions-Leucocytic infiltrate is not only reduced in number but its distinct phenotype compared with controls implies a reduced activation status of infiltrating monocytes to accompany increased IL-10 and reduced IFN-production in tolerised animals. This modulation may in turn contribute towards protection against target organ destruction in EAU. (Br J Ophthalmol 1999;83:478-485) Diminishing tissue destruction in organ specific autoimmune diseases by mucosal administration of autoantigen is potentially a powerful method of immunosuppression. Methods-Female

Nasal antigen administration successfully suppresses a model of organ-specific autoimmune disease, experimental autoimmune uveoretinitis (EAU)

Methods: Female Lewis rats were immunised with retinal extract (RE) and then treated as follows. Group 1 received no specific therapy and served as control; group 2 were fed CsA from day 7 to day 20 post immunisation; group 3 received inhalational tolerance therapy with RE in addition to CsA; tolerance therapy was continued after day 20 when CsA was stopped.Experiments varying the timing and dosage of both tolerising and immunising antigen were also performed, the details of which are described. Incidence, day of onset and clinical activity were recorded and histo pathological assessment of intraocular inflammation, in particular the extent of autoimmune target-organ damage, was graded semiquantitatively.