Recoverin: a potent uveitogen for the induction of photoreceptor degeneration in Lewis rats.
Recoverin is a calcium-binding protein identified as an autoantigen in a paraneoplastic degenerative disease of the human retina known as cancer-associated retinopathy (CAR). In this study we investigated whether recoverin could elicit an immune response leading to the degeneration of photoreceptor cells in a rodent retina, and whether an animal model of CAR could be developed. Injection of Lewis rats with recoverin caused degeneration of the photoreceptor cells. Several features of uveoretinitis were observed, including vitreous cells, perivasculitis, retinal lesions and complete loss of the photoreceptor cell layer. The first clinical signs of retinal inflammation were observed 10-14 days after immunization. The earliest histological changes in the retina also were observed 14 days after immunization. Infiltration of the photoreceptor cell layer and inner layers of the retina with lymphocytic and some polymorphonuclear cells was frequently observed. Photoreceptors were damaged and later fully degenerated. This sequence of events was associated with high antibody titers against recoverin in all animals tested. Cellular responses to recoverin assayed between days 7 and 28 after immunization showed strong in vitro proliferative activities to recoverin. In addition, all aspects of the degenerative events could be reproduced in naive animals by the adoptive transfer of stimulated lymphocytes obtained from animals previously immunized with recoverin. This study demonstrates the successful induction of photoreceptor degeneration using recoverin as an immunogen. We demonstrate that recoverin is both a potent antigen and uveitogen. These observations may be relevant to our understanding of CARs in humans.
Adamus
G
G
R.S. Dow Neurological Sciences Institute, Good Samaritan Hospital and Medical Center, Portland, OR 97209.
Ortega
H
H
Witkowska
D
D
Polans
A
A
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D002135:Calcium-Binding Proteins / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005136:Eye Proteins; D051597:Hippocalcin; D008074:Lipoproteins; D008213:Lymphocyte Activation; D009419:Nerve Tissue Proteins; D051381:Rats; D011917:Rats, Inbred Lew; D051603:Recoverin; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000209:etiology; D013601:T-Lymphocytes / Q000276:immunology; D014605:Uveitis / Q000209:etiology / Q000473:pathology
D000951:Antigens, Neoplasm; D002135:Calcium-Binding Proteins; D005136:Eye Proteins; D008074:Lipoproteins; D009419:Nerve Tissue Proteins; C496733:Rcvrn protein, rat; D051603:Recoverin; D051597:Hippocalcin