INTRANASAL ADMINISTRATION OF RETINAL ANTIGENS SUPPRESSES RETINAL ANTIGEN-INDUCED EXPERIMENTAL AUTOIMMUNE UVEORETINITIS

Bovine retinal extract (RE) is a heterologous mixture of highly uveito genic proteins including S-Antigen (S-Ag), interphotoreceptor retinol binding protein (IRBP) and rhodopsin, and is a potent inducer of exper imental autoimmune uveoretinitis (EAU). Intranasal inoculation of Lewi s rats with RE performed daily for 10 days prior to immunization with RE suppresses both the severity and the incidence of the clinical resp onse and histopathological changes in EAU. Significant suppression of the disease in treated animals could be achieved with a total (cumulat ive) intranasal inoculum of 42 mu g of antigen. Animals which were tre ated with extract exhibited a normal total antibody response to S-Ag, IRBP and retinal extract when compared with controls [phosphate-buffer ed saline (PBS) treated] animals. The antibody response in tolerized a nimals was predominantly anti-S-Ag IgG2a with suppression of anti-S-Ag IgM response. Treated animals had a significantly suppressed delayed- type hypersensitivity (DTH) response to retinal extract but normal res ponse to purified protein derivative (PPD) compared to control animals . Adoptive transfer of splenocytes from treated animals also demonstra ted some protection against RE-induced EAU. These results demonstrate that tolerance induction impairs the onset and severity of EAU by inhi biting the DTH response to heterologous mixture of retinal antigens.