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Shinji Ueno, Koji Miura Nishiguchi, Hiroko Terasaki; Degeneration of retinal ON bipolar cells induced by serum including autoantibody against TRPM1 in mouse model of paraneoplastic retinopathy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4172.
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© ARVO (1962-2015); The Authors (2016-present)
Evidence has been obtained that the transient receptor potential melastatin 1 (TRPM1) protein was the antigen for the autoantibody against ON bipolar cells in PR patients. The purpose of this study was to determine whether the serum of a PR patient with the TRPM1 antibody will cause a degeneration of ON bipolar cells.
Seventy C57BL/6 mice at 7-10 weeks-old-age were used. Sera were collected from one PR patient with TRPM1 antibody and one visually normal male subject. Mice were anesthetized with ether, and 1 µL of the serum of the patient was injected intravitreally into one of the eyes and serum from the control into the other eye of C57BL/6 mice. Electroretinogram (ERG) and histopathological analysis including immuhohistochemical analysis and transmission electron microscopic examination were performed.
The electroretinograms (ERGs) of the mice were altered acutely after the injection, and the shape of the ERGs resembled that of the patient with PR. Histological analysis showed that some of the bipolar cells were apoptotic by 5 hours after the injection, and degenerated bipolar cells were found 3 days later to be engulfed by macrophages. At 3 months, the inner nuclear layer was thinner and the amplitudes of the ERGs were still reduced.
Our results indicate that the serum of a patient with PR contained an antibody against TRPM1 that led to an acute death of retinal ON bipolar cells.
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