AI Article Synopsis
- Melanoma-associated retinopathy (MAR) is linked to malignant melanoma and features autoantibodies against TRPM1, a channel in melanocytes and retinal cells; this study aimed to identify specific regions of the TRPM1 that these autoantibodies target.
- Researchers used patient blood samples to perform tests on modified cells and mouse retinas, successfully determining that MAR autoantibodies recognize a specific part of the TRPM1 gene associated with exons 9 and 10.
- The findings suggest that TRPM1 autoantibodies may be produced in response to abnormal proteins due to an alternative TRPM1 mRNA variant from melanoma, with potential implications for understanding visual symptoms in MAR patients related to TR
Article Abstract
Purpose: Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome associated with malignant melanoma and the presence of anti-retinal autoantibodies, including autoantibodies against transient receptor potential melanopsin 1 (TRPM1), a cation channel expressed by both melanocytes and retinal bipolar cells. The goal of this study was to further map the antigenic epitope.
Methods: Patient sera were tested by immunofluorescence and Western blotting on HEK293 cells transfected with enhanced green fluorescent protein (EGFP)-TRPM1 fusion constructs and mouse retina sections.
Results: The epitope recognized by MAR patient sera was mapped to a region encoded by exons 9 and 10 of the human TRPM1 gene. This region of TRPM1 is highly conserved with TRPM3, and indeed MAR sera were found to cross-react with TRPM3, a closely related channel expressed in the retinal pigment epithelium (RPE).
Conclusions: These results indicate that TRPM1 autoantibodies in MAR patient sera recognize a short, intracellular segment of TRPM1. Cross-reactivity with TRPM3 in the RPE may account for other visual symptoms that are experienced by some MAR patients such as retinal and RPE detachments. We propose that TRPM1 autoantibodies are generated in response to abnormal TRPM1 polypeptides encoded by an alternate mRNA splice variant expressed by malignant melanocytes.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455167 | PMC |
| http://dx.doi.org/10.1167/iovs.17-21443 | DOI Listing |
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