Human melanoma-associated retinopathy (MAR) antibodies alter the retinal ON-response of the monkey ERG in vivo

PURPOSE. Melanoma-associated retinopathy (MAR) is a paraneoplastic conditio n that causes visual symptoms of night-blindness and photopsias. The electr oretinogram (ERG) of MAR patients is characteristically abnormal in a way t hat implicates retinal depolarizing bipolar cell (DBC) dysfunction. Whether an injection of Ige from MAR patients into the vitreous of monkeys would a lter the ERG acutely as a demonstration of a. functional basis for patients ' visual symptoms was explored. METHODS. MAR IgG was isolated from three visually symptomatic melanoma pati ents. Control IgG was from melanoma patients with no vision problems. The E RG was monitored after intravitreal injections into monkey eyes. One eye wa s injected with 2-amino-4-phosphonobutyric acid (APB), which is known ro bl ock DEC ON-pathway responses. Retinal immunocytochemistry was performed usi ng fluorescein isothiocyanate-labeled goat anti-human IgG. RESULTS. Within 1 to 3 hours after MAR IgG injection, the ERG photopic b-wa ve was diminished, with far less effect on the a- and d-waves. These change s are characteristic of DEC dysfunction and were similar to the effects of APB. The scotopic ERG b-wave, which reflects activity of rod-driven DBCs, s howed a loss of amplitude and threshold sensitivity after MAR IgG. Retinal immunocytochemistry with anti-IgG antibody showed IgG penetration throughou t the retinal layers, but staining was not specific for a single type of re tinal neuron. CONCLUSIONS. Intravitreal injection of human MAR IgG altered the monkey ERG acutely in ways that implicate functional disruption of retinal DEC signal ing. These results support the hypothesis that MAR IgG circulating antibodi es are responsible for the reported visual symptoms. Bipolar cells in the O N-pathway appear to be affected more than OFF-pathway bipolar cells of the cone pathway in this acute preparation.