Passive administration of antibody against retinal S-antigen induces electroretinographic supernormality

Electroretinographic supernormality, affecting both the a- and b-waves of the electroretinogram (ERG), occurs consistently before the onset of experimental autoimmune uveoretinitis (EAU) in rabbits and rats. To investigate the possible role of antibody to S-antigen (S-ab) in this phenomenon, affinity-purified polyclonal rat S-ab was injected intravenously into normal rats and administered to isolated rat eyecup preparations by bolus perfusion. In both situations, ERG supernormality was observed. The effect in vivo peaked 90 min after injection, and ERG changes in vitro were observed within 15 sec. The ERG response in vivo and in vitro was dose dependent and was abolished in vivo by pretreatment with cyproheptadine (a serotonin antagonist). The ERG was not affected in either system by a control rat antibody (antiovalbumin) or by murine monoclonal or rabbit polyclonal antibodies to S-antigen. The induction of ERG supernormality in vivo and in vitro by homologous S-ab indicates the operation of species-specific mechanisms both involving and bypassing the blood-retinal barrier and highlights a significant role for humoral autoimmunity in the pathogenesis of S-antigen-induced EAU in the rat.