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Charles E. Thirkill; A Line of Identity - The 45 kd CAR Antigen. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1844.
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© ARVO (1962-2015); The Authors (2016-present)
Vision loss in cancer patients may include an immune-mediated paraneoplasia initiated by a malignancy located distant from the eye. In recent years, continuing inquiry has lead to the identification of an increasing number of retinal antigens involved in the process of cancer-associated retinopathies (CAR), and Melanoma Associated Retinopathies (MAR). The subject of this project, a 45 kd retinal antigen was identified in the abnormal immunologic activity of three retinopathy patients, two of whom were known to have cancer, the third only later found to have cancer. The intent of this project is to isolate, identify, and characterize this unknown, disease-associated ocular antigen, to determine its potential value as an novel means of detecting an antigenically distinct subset of CAR.
Western blot reactions of an extract of pig retina were used to compare the antibody activity of the three unusual patients suspected of experiencing a paraneoplastic retinopathy. Comparisions were made with three patients having a history of steroid-responsive idiopathic retinopathies, and three normal human volunteers. The 45 kd retinal component was isolated by electrophoresis and subjected to proteomic analysis. Indirect immuno-histochemistry on sectioned rhesus monkey eye was used to locate the expression of the antigen within the complex neurosensory retina.
Expression of the 45 kd antigen within the retina is confined to components of the outer segments of the photoreceptor layer. The 45 kd reaction was found in the immunologic activity of the three patients suspected of experiencing a paraneoplastic retinopathy. No comparable immunologic activity was found in the idiopathic retinopathy patients, or normal volunteers. Proteomic analysis provides preliminary evidence that the 45 kd antigen is a member of the ocular arrestin family, known to be expressed in the outer segmens, with some memebrs incriminated in aberrant expressions in cancers.
Paraneoplastic retinopathies are known to involve a growing collection of ocular antigens. The 45 kd photoreceptor antigen, currently found reactive only in the abnormal immunologic activity of retinopathy patients with gynecologic cancer, is proposed as an additional example of CAR, seemingly confined to vision loss in ovarian cancer patients. Members of the arrestin family are known to be expressed by malignancies, but further work is required to determine if the 45 kd abnormality described here is limited to ovarian cancers. Continuing pursuit of the precise identity of the 45 kd antigen includes efforts to clone the gene responsible for its expression from a cDNA library of human retina.
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