This project is aimed at learning about the pathogenesis of immune-mediated eye diseases. The main effort has been focused on investigating an animal disease, experimental autoimmune uveitis (EAU), which is considered a model for certain eye diseases in man. The main findings of the present studies include: (1) A retinal component, interphotoreceptor retinoid binding protein (IRBP), was found to be highly uveitogenic in experimental animals. Indeed, IRBP was found to be at least as efficient in inducing EAU in rats or monkeys as the well known S-antigen (S-Ag). The experimental disease induced by IRBP resembles grossly that induced by S-Ag, both in the eye and the pineal gland. The two diseases differ, however, in the pattern of responsiveness among rats with different genetic makeups. Rats of the BN and related strains are """"""""low responders"""""""" to EAU induced by S-Ag, but are """"""""high responders"""""""" when tested for EAU induced by IRBP. The finding that the retina contains a second major uveitogenic molecule, in addition to S-Ag, is of importance since (a) IRBP may participate in the etiology of certain uveitic conditions in man and (b) the animal disease it induces provides useful new data on immunopathogenic mechanisms in the eye. (2) Induction of EAU by S-Ag or IRBP is highly facilitated by an additional adjuvant, the B. pertussis bacteria (see also our Reports for FY 1982, 1983). The effect of the whole bacteria was found to be produced by a purified component, designated pertussis toxin (Ptx). Treatment of rats with Ptx reduced the threshold amount of S-Ag needed for induction of EAU, shortened the onset time and produced more severe pathologic changes. The mode of action of Ptx was further analyzed. Adoptive transfer of EAU was enhanced by Ptx treatment of the donor rats, but not by treatment of the recipient. These results suggest that Ptx enhances EAU development mainly by affecting the process of lymphocyte sensitization toward the uveitogenic antigen.
Showing the most recent 10 out of 21 publications