Complement proteins in the retina in cancer-associated retinopathy
JAMA Ophthalmology Nov 08, 2019
Dryja TP, et al. - Researchers performed this case series study to determine complement proteins in the retina in cancer-associated retinopathy (CAR), a paraneoplastic syndrome typically related to autoantibodies against cancer antigens that cross-react with antigens in the retina. From a deceased patient with CAR, archived paraffin blocks of an eye were retrieved. Negative controls were sections of normal (without CAR) human eyes (obtained from Lions Eye Bank) and positive controls were normal human liver cells (obtained from Avaden). Complement factors C3 (LS-B13028), C9 (LS-B4849), and B (LS-B13829) were investigated using antibodies. In an eye with CAR, the presence of complement factors in or around the degenerating photoreceptor inner and outer segments and the retinal pigment epithelium (RPE) was found. Especially, the presence of C3 and C9 in the photoreceptors and the RPE was detected. Of the classical complement pathway stimulated by antibody-antigen complexes on cell surfaces, C3 and C9 constituted the fundamental components. Evidence for one of the suggested mechanisms of photoreceptor loss in CAR was generated in this study. Following the attachment of autoantibodies to photoreceptor cells, activation of the classical complement pathway happens which causes cell lysis mediated by the membrane attack complex, of which C9 represents a principal component. The possibility of a protective effect of complement inhibitory proteins, expressed by the RPE, on the RPE was also suggested.
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