Pilot Project Abstract - Morgans, Catherine, PhD

Morgans, Catherine, PhD, Associate Professor, Dept. of Ophthalmology, OHSU

“Identification of the retinal bipolar cell antigen causing melanoma-associated retinopathy”

This grant will investigate an antigen expressed by both melanocytes and retinal ON-bipolar cells that we predict is the target of an autoimmune response causing visual deficits experienced by some melanoma patients.

Melanoma-associated retinopathy (MAR) is a condition experienced by some melanoma patients, believed to be caused by an autoimmune response to retinal antigens expressed by the tumor. The visual deficits include a "shimmering light" effect, night blindness, and a progressive loss of vision. Electroretinogram recordings from many of these patients indicate a block in visual processing at the bipolar neurons in the retina, and serum from these patients contains antibodies that label retinal bipolar cells. Furthermore, the titer of the bipolar cell antibody appears to be directly related to the stage of the melanoma, with higher antibody activity being associated with advanced stages of the disease. Identification of the bipolar cell antigen is essential to understanding the link between melanoma and vision loss. On a clinical level, identification of the bipolar cell antigen will lead to the development of ELISA assays to identify melanoma patients at risk for MAR, allowing early intervention. An assay for the bipolar cell antigen could also be used with other diagnostic procedures in assessing the stage of a patient's melanoma. Morgans and her colleagues have recently identified a TRP ion channel in retinal bipolar cells that is also expressed by melanocytes. The gene encoding this channel has previously been shown to be down-regulated in highly metastatic melanomas. This grant will test the hypothesis that this TRP channel is the bipolar cell antigen causing MAR.