title: Cancer-retina antigens as potential paraneoplastic antigens in melanoma-associated retinopathy.
abstract: Melanoma-associated retinopathy is a rare paraneoplastic neurological syndrome characterized by retinopathy in melanoma patients. The main photoreceptor proteins have been found to be expressed as cancer-retina antigens in melanoma. Here we present evidence that these can function as paraneoplastic antigens in melanoma-associated retinopathy. Sera and one tumor cell line of such patients were studied and ret-transgenic mice spontaneously developing melanoma were used as a murine model for melanoma-associated retinopathy. Splenocytes and sera were used for adoptive transfer from tumor-bearing or control mice to wild-type mice. Retinopathy was investigated in mice by funduscopy, electroretinography and eye histology. Expression of photoreceptor proteins and autoantibodies against arrestin and transducin were detected in melanoma-associated retinopathy patients. In tumor-bearing ret-transgenic mice, retinopathy was frequently (13/15) detected by electroretinogram and eye histology. These pathological changes were manifested in degenerations of photoreceptors, bipolar cells and pigment epithelium as well as retinal detachment. Mostly these defects were combined. Cancer-retina antigens were expressed in tumors of these mice, and autoantibodies against arrestin were revealed in some of their sera. Adoptive transfer of splenocytes and sera from tumor-bearing into wild-type mice led to the induction of retinopathy in 4/16 animals. We suggest that melanoma-associated retinopathy can be mediated by humoral and/or cellular immune responses against a number of cancer-retina antigens which may function as paraneoplastic antigens in melanoma-associated retinopathy.
authors.affiliation: Skin Cancer Unit, German Cancer Research Center, Heidelberg and University Hospital, Mannheim, Germany.
authors.forename: Alexandr V
authors.initials: AV
authors.lastname: Bazhin
authors.forename: Claudia
authors.initials: C
authors.lastname: Dalke
authors.forename: Nadine
authors.initials: N
authors.lastname: Willner
authors.forename: Oliver
authors.initials: O
authors.lastname: Abschütz
authors.forename: Hannes G H
authors.initials: HG
authors.lastname: Wildberger
authors.forename: Pavel P
authors.initials: PP
authors.lastname: Philippov
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Jochen
authors.initials: J
authors.lastname: Graw
authors.forename: Martin Hrabé
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.forename: Viktor
authors.initials: V
authors.lastname: Umansky
authors.forename: Stefan B
authors.initials: SB
authors.lastname: Eichmüller
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004596:Electroretinography / Q000379:methods; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000276:immunology / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000150:complications* / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010257:Paraneoplastic Syndromes / Q000150:complications / Q000276:immunology* / Q000473:pathology; D012160:Retina / Q000378:metabolism*; D012164:Retinal Diseases / Q000150:complications* / Q000276:immunology* / Q000473:pathology