Autoantibodies in Melanoma-Associated Retinopathy Recognize an Epitope Conserved Between TRPM1 and TRPM3

Robert Duvoisin, Tammie L. Haley, Gaoying Ren, Iwona Strycharska-Orczyk, James P. Bonaparte, Catherine Morgans

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

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).

Original languageEnglish (US)
Pages (from-to)2732-2738
Number of pages7
JournalInvestigative ophthalmology & visual science
Volume58
Issue number5
DOIs
StatePublished - May 1 2017

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Ocular Paraneoplastic Syndromes
Autoantibodies
Epitopes
Retinal Pigment Epithelium
Melanocytes
Serum
Retinal Bipolar Cells
Paraneoplastic Syndromes
melanopsin
HEK293 Cells
Fluorescent Antibody Technique
Retina
Cations
Exons
Melanoma
Western Blotting

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Autoantibodies in Melanoma-Associated Retinopathy Recognize an Epitope Conserved Between TRPM1 and TRPM3. / Duvoisin, Robert; Haley, Tammie L.; Ren, Gaoying; Strycharska-Orczyk, Iwona; Bonaparte, James P.; Morgans, Catherine.

In: Investigative ophthalmology & visual science, Vol. 58, No. 5, 01.05.2017, p. 2732-2738.

Research output: Contribution to journalArticle

Duvoisin, Robert ; Haley, Tammie L. ; Ren, Gaoying ; Strycharska-Orczyk, Iwona ; Bonaparte, James P. ; Morgans, Catherine. / Autoantibodies in Melanoma-Associated Retinopathy Recognize an Epitope Conserved Between TRPM1 and TRPM3. In: Investigative ophthalmology & visual science. 2017 ; Vol. 58, No. 5. pp. 2732-2738.
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