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DG Green, H Guo, D-AM Pillers; Depolarizing Bipolar Cell Activity in Isolated Retina of the MdxCV3cv3 Mouse Supports Role of Dystrophin in Synaptic Transmisssion . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3765.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The mdxcv3 mouse is a good model for the retinal changes seen in Duchenne muscular dystrophy (DMD). The reduced amplitude of the b-wave found in both these mice and in DMD patients suggests abnormal inner nuclear layer function. To assess depolarizing bipolar cell function in these mice we have recorded electroretinograms (ERGs) from pieces of isolated retina and measured the ability of the glutamate analog APB, which blocks depolarizing bipolar cells, to suppress the b-wave. Methods: Pieces of dark-adapted retina from either mdxcv3 or C57BL/6J retinas were superfused with an oxygenated Ringer solution at 36 - 37 ° C. Using two extracellular microelectrodes, one touching the tips of the photoreceptor outer segments and the other on the vitreal side of the retina, transretinal ERGs to flashes of light were recorded. The ability of DL2-amino-4-phosphonobutyric acid (APB) to block the b-wave was assessed by adding various concentrations of APB (0.625 to 50 µ M) to the perfusate. Results: We have recorded ERGs from isolated pieces of mdxcv3 retina. As reported for the intact animals, these ERGs differ from those from those of normal control retinas in that they show reduced b-wave amplitudes, and increased b-wave implicit times. Moreover, we find that the mdxcv3 retina is more sensitive to APB than control retinas. That is the b-wave is blocked by concentrations of APB that are 7-10 times lower than in controls. Conclusion: APB selectively blocks the responses of depolarizing bipolar cells by binding to sites on the post-synaptic membrane. The ability of lower concentrations of APB to block the b-wave in mdxcv3 suggests that there are changes in the glutamate binding sites on the post-synaptic membrane of depolarizing bipolar cells in these animals. Synaptic transmission from photoreceptors to depolarizing bipolar cells is abnormal in the mdxcv3 retina. Dystophin may play a role in establishing the specificity and selectivity of the metabotrophic glutamate receptors on depolarizing bipolar cells.
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