Localization of a Uveitogenic Soluble Retinal Antigen in the Normal Guinea Pig Eye by an Indirect Fluorescent Antibody Technique

Abstract

Since immunization of guinea pigs with homologous retina can elicit experimental allergic uveitis concomitant with development of tissue specific antibodies, an attempt was made to localize a uveitogenic soluble retinal antigen in the normal guinea pig eye by an indirect fluorescent antibody method. Specific green fluorescence was seen in the outer portions of the retina, surrounding the nuclei of the outer nuclear layer and extending in both directions outward to the outer limbs of the photoreceptor cells and inward to the outer plexiform layer. This specific fluorescence was not detectable in other ocular structures, notably the uvea. Use of a homologous system in an indirect fluorescent antibody technique also resulted in a demonstration, by FA anti-GP, of distribution of γ-globulins in the normal guinea pig eye. Green fluorescence due to γ-globulins was seen brightly in the corneal stroma and in the connective tissue external to the sclera, less brightly and diffusely throughout the uvea, very faintly in the vitreous, and not at all in the retina. The demonstration of normal γ-globulins by this procedure did not interfere with the detection of tissue specific antigen. The relationship of antigen in the retina to possible mechanisms of autoimmune uveal disease is discussed.

Autoimmune Uveo-Retinitis in the Rat Sensitized with Retina Photoreceptor Cell Antigen

“…These differences in ocular manifestations in the two species can be correlated with differences in the hematogenous routes by which the in flammatory infiltrates reach the ocular target. In both rats and guinea pigs [2], the antigen responsible for the ocular pathology has been identified by fluorescent antibody staining as a constituent of the photoreceptor cells, which are ultimately invaded and destroyed by the cellular infil trates [8]. The source of these inflammatory cells in the guinea pig, whose retina is avascular except for a few fine vessels at the optic disc, is the choroidal circulation.…”

“…The sera were examined for the presence of autoantibodies reactive with rat retina by the indirect immunofluorescent tech nique, as previously described [2], …”

“…The term experimental allergic uveitis was introduced in 1965 to de scribe the autoimmune ocular disease produced in the guinea pig by sensi tization with homologous retina [5], Although the possibility was raised that this anomaly may be due to antigens shared by uvea and retina [1,5], subsequent studies established that the pathogenic antigen is retina specific [6,7,9], and is a protein constituent of the retina located in the photoreceptor cell layers [2,10], These findings have raised questions concerning the mechanisms by which sensitization to retina antigen re sults in uveitis.…”

“…Depending upon the species used, there are two possible vascular pathways for inflammatory infiltration of the antigenic locus in the photo receptor cells [2], the uveal circulation and the retinal circulation. Unlike most species used thus far in studies of this experimental disease, the rat has well developed vascular systems in both of these ocular tissues.…”

Relationship of the Primary and Secondary Immune Response to Induction and Relapse of Experimental Allergic Uveitis with Retina Antigen

“…The experimental disease is associated with both humoral and cellu lar responses to a protein antigen located in the retina photoreceptor cells [7,16,19]. Although the cellular response has been implicated in the mechanisms of the tissue pathology [3], the humoral response plays an undetermined role in the host reaction.…”