Experimental autoimmune retinitis in the rat induced by immunization with rhodopsin: an ultrastructural study.
Experimental autoimmune retinitis induced by immunization with rhodopsin was investigated in the Lewis rat using transmission electron microscopy and light microscopy. The first signs of retinitis consisted of scattered infiltrations of lymphocytes and other mononuclear cells, predominantly in the inner nuclear layer and outer plexiform layer. Occasionally, some macrophages were detected in the photoreceptor cell layer. Eyes exhibiting a clinically moderate or severe inflammation contained areas of normal retina coexistent with mildly to severely inflamed foci. The central retina was more frequently affected than the peripheral area. In moderately inflamed foci, macrophages infiltrated the photoreceptor cell layer, damaging and eliminating its structures. Inflammatory cells penetrated the photoreceptor outer segment layer which remained unaltered so far in spite of a high serum anti-(rhod)opsin antibody titer. In stages of severe inflammation, massive infiltrations of macrophages and polymorphonuclear cells destroyed the photoreceptor cells focally, leaving the retinal pigment epithelium virtually unaffected. Adjacent to these foci the pigment epithelial cells sometimes exhibited increased numbers of phagosomes and swelling. The locations of the cell infiltrations and lesions in progressive stages of development suggest that the rod outer segments are the target for the autoimmune damage. The described patterns of inflammation were compared with those of previous studies using other animal species and inciting antigens. Especially in rhodopsin-induced retinitis, the blood-retina barrier at the level of the Bruch's membrane/pigment epithelium appears to be highly resistant to cytotoxic cells. The present observations are in agreement with the concept that the cellular immune response plays a major role in the pathogenesis of (rhod)opsin-induced retinitis.
Institute of Ophthalmology, University of Nijmegen, The Netherlands.
R M
RM
Broekhuyse
J H
JH
Stekhoven
M
M
Arends
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000473:pathology*; D005260:Female; D007111:Immunity, Cellular; D007114:Immunization; D008264:Macrophages / Q000276:immunology; D008854:Microscopy, Electron; D010786:Photoreceptor Cells / Q000648:ultrastructure; D010857:Pigment Epithelium of Eye / Q000648:ultrastructure; D051381:Rats; D011917:Rats, Inbred Lew; D012160:Retina / Q000648:ultrastructure; D012173:Retinitis / Q000276:immunology / Q000473:pathology*; D012243:Rhodopsin / Q000276:immunology*
D001324:Autoantigens; D012243:Rhodopsin