Abstract
Purpose :
Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome associated with cutaneous malignant melanoma (CMM). Visual symptoms include night blindness, photopsia and reduced contrast sensitivity. An abnormal electroretinogram (ERG) b-wave and the presence of anti-bipolar cell autoantibodies, including autoantibodies reacting with the ON-bipolar cell TRPM1 channel, help to confirm the diagnosis. The goal of this study was to determine if CMM patients without visual symptoms also express anti-TRPM1 autoantibodies and if they are at risk of developing MAR.
Methods :
Serum samples from 15 CMM patients without declared visual symptoms were tested using three assays: immunofluorescent labeling of TRPM1-transfected HEK cells, immunofluorescent labeling of retinal sections from wild-type and TRPM1 knockout mice, and immunoblot detection of a bacterially produced recombinant TRPM1 polypeptide. Real-time PCR of two TRPM1 encoding cDNA segments was used to examine mRNA splicing in CMM tumor biopsies.
Results :
Autoantibodies against TRPM1 are present in sera from CMM patients without reported visual symptoms. While the numbers are too small to reach significance, it appeared that these patients had a better prognosis than those whose serum was negative for TRPM1 immunoreactivity. TRPM1 splicing variants may encode polypeptides that adopt new, antigenic conformations, which could explain the generation of TRPM1 autoantibodies
Conclusions :
Serum samples from 15 CMM patients without declared visual symptoms were tested using three assays: immunofluorescent labeling of TRPM1-transfected HEK cells, immunofluorescent labeling of retinal sections from wild-type and TRPM1 knockout mice, and immunoblot detection of a bacterially produced recombinant TRPM1 polypeptide. Real-time PCR of two TRPM1 encoding cDNA segments was used to examine mRNA splicing in CMM tumor biopsies.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.