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Bo Lei, Ronald A. Bush, Ann H. Milam, Paul A. Sieving; Human Melanoma-Associated Retinopathy (MAR) Antibodies Alter the Retinal ON-Response of the Monkey ERG In Vivo. Invest. Ophthalmol. Vis. Sci. 2000;41(1):262-266.
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purpose. Melanoma-associated retinopathy (MAR) is a paraneoplastic condition
that causes visual symptoms of night-blindness and photopsias. The
electroretinogram (ERG) of MAR patients is characteristically abnormal
in a way that implicates retinal depolarizing bipolar cell (DBC)
dysfunction. Whether an injection of IgG from MAR patients into the
vitreous of monkeys would alter 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 patients.
Control IgG was from melanoma patients with no vision problems. The ERG
was monitored after intravitreal injections into monkey eyes. One eye
was injected with 2-amino-4-phosphonobutyric acid (APB), which is known
to block DBC ON-pathway responses. Retinal immunocytochemistry was
performed using fluorescein isothiocyanate–labeled goat anti-human
results. Within 1 to 3 hours after MAR IgG injection, the ERG photopic b-wave
was diminished, with far less effect on the a- and d-waves. These
changes are characteristic of DBC dysfunction and were similar to the
effects of APB. The scotopic ERG b-wave, which reflects activity of
rod-driven DBCs, showed a loss of amplitude and threshold sensitivity
after MAR IgG. Retinal immunocytochemistry with anti-IgG antibody
showed IgG penetration throughout the retinal layers, but staining was
not specific for a single type of retinal neuron.
conclusions. Intravitreal injection of human MAR IgG altered the monkey ERG acutely
in ways that implicate functional disruption of retinal DBC signaling.
These results support the hypothesis that MAR IgG circulating
antibodies are responsible for the reported visual symptoms. Bipolar
cells in the ON-pathway appear to be affected more than OFF-pathway
bipolar cells of the cone pathway in this acute
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