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 wildtype 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 wildtype 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. '

RETRACTED ARTICLE: cGMP-phosphodiesterase 6, transducin and Wnt5a/Frizzled-2-signaling control cGMP and Ca2+ homeostasis in melanoma cells

“…Among these, PDE6 is expressed at a high frequency. Such expression of cancer-retina antigens could generate an autoimmune response [8], which in turn might lead to development of a paraneoplastic neurological syndrome, melanoma-associated retinopathy [9]. Furthermore, we demonstrated that expression of cancer-retina antigens can be modulated by light as it proceeds in photoreceptor cells [10].…”

Paraneoplastic and non-paraneoplastic retinopathy and optic neuropathy: Evaluation and management

“…For example, antibodies against a 35-kDa Muller cell protein, 76 a 22-kDa neuronal antigen found in both the retina and optic nerve, 129 and a novel membrane-associated 33-kDa protein 205 have all been described in MAR. Because visual phototransduction proteins are known to be produced by melanoma cells, it should come as no surprise that autoantibodies against transducin-a, 2 transducin-b, 225 arrestin, 27 and rhodopsin 98 are found in MAR patients. The wide diversity of retinal antigens encountered is likely indicative of the immunologic heterogeneity of this disorder.…”

Autoimmune Retinopathy

“…Some patients with MAR have been found to express a variety of autoantibodies against various proteins including transducin-β [11], rhodopsin [47], arrestin [48], a 35-kDa protein in Müller glial cells, a 22-kDa neuronal antigen, mitofilin, titin and COX [49]. Mitofilin is a mitochondrial protein anchored in the inner mitochondrial membrane, presumed to influence the morphological structure and function of mitochondria [49].…”