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John Demirs, Vivian Lee, Thaddeus P Dryja; Evidence of complement involvement in cancer-associated retinopathy (CAR). Invest. Ophthalmol. Vis. Sci. 2018;59(9):3148.
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Cancer-associated retinopathy is a paraneoplastic syndrome thought to be caused by autoantibodies against cancer antigens that cross-react with antigens in the retina. The autoantibodies presumably destroy photoreceptor cells via the classical complement pathway. To our knowledge, there is no published study with evidence of complement pathway activation in the disease. We searched for complement proteins in an affected eye.
We evaluated paraffin sections from an affected eye of a deceased patient who was previously reported (Goldstein et al., Arch Ophth 117:1641-1645, 1999). Controls were obtained from the Lions Eye Bank Institute and normal human liver was obtained from Avedan. We tested antibodies from Lifespan Biosciences that recognize complement factors C3 (LS-B13028), C9 (LS-B4849) and factor B (LS-B13829). We used immunohistochemical protocols that were modifications of a standard Ventana IHC protocol. Antibodies were chromatically visualized with diaminobenzidine or alkaline phosphatase.
As expected, in sections of a normal human liver the antibodies against C3, C9, and factor B detected antigen in liver cells. In sections of a normal human eye, none of the antibodies detected antigens in the retina or retinal pigment epithelium (RPE), while the anti-C9 antibody highlighted only Bruch’s membrane. In the eye with cancer-associated retinopathy, most of the retina had no photoreceptor cells, and the inner nuclear layer was adjacent to the RPE. A few areas had small patches of remaining photoreceptors. Based on the respective antibodies’ staining patterns, the remaining photoreceptor outer segments had clearly detectable C3 but not C9. Factor B staining was inconclusive. The apical aspect of many RPE cells had C3 and C9, but not factor B. The cytoplasm of many RPE cells had C3 and C9. Bruch’s membrane had C9. The endothelium of choroidal blood vessels had C3.
In cancer-associated retinopathy, complement factors, especially C3, appear to be present in the degenerating photoreceptor outer segments and RPE. Our findings suggest that the complement pathway plays a role in this disease.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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