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Bo Lei, Yu Liu, Tao Lin, Hongxia Yang; Exogenous zinc ions interrupt visual signal transmission from photoreceptors to bipolar cells and reduce retinal TRPM1 expression in mouse. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2672.
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Transient receptor potential cation channel subfamily M member 1 (TRPM1) on the retinal ON-bipolar cells plays a crucial role in visual transmission. Previous studies indicated zinc ions were inhibitors of TRPM1 in vertebrate in vitro. We determined whether zinc affected retinal signal transmission in mammals through inhibition of TRPM1.
C57BL/6 mice were randomly divided into control and experimental groups. The experimental mice received unilateral intravitreal injections of 0.4 μl 0.01M zinc sulfate solution and the control mice received injections of same volume of PBS. Dark- and light-adapted electroretinogram (ERG) was recorded at 1 hour, 1 day, 1 week, 4 weeks and 8 weeks after injection. Western blotting was employed to assay TRPM1 protein expressions in the retina. PKCα and CtBP2 immunofluorescence was performed to detect the morphologic changes of rod bipolar cells and photoreceptor synaptic structures. In addition, 50 μl of 0.05 M zinc sulfate solution was injected intravitreally in a rhesus monkey. ERG ON-OFF responses were recorded at 2 hours after injection.
From 1 hour to 8 weeks after zinc injections, the mouse ERGs exhibited similar changes and a negative ERG waveform was evident: the amplitudes of dark- and light-adapted ERG b-waves were dramatically decreased while the a-waves appeared normal. Similar ERGs were also observed in the zinc-injected monkey eye. Furthermore, the ON-OFF ERG responses of the monkey showed a prominently attenuation of the b-wave but a unaffected a-wave. Western blotting indicated TRPM1 protein expression was decreased in the zinc-treated mouse retina. Morphology showed retinal structures were unchanged at day 1 after zinc injection. However, at 8 weeks after injection, the inner retina particularly the inner nuclear layer (INL) became thinner, the number of rod ON bipolar cell decreased. Meanwhile, aberrant dendritic processes of rod bipolar cells projected into the outer nuclear layer (ONL). The number of the photoreceptor synaptic ribbon decreased and ectopic ribbons were seen in the ONL of zinc-treated retina.
Exogenous zinc ions interrupted retinal signal transmission from the photoreceptors to the ON bipolar cells but barely affected photoreceptor functions. TRPM1 appeared to be the target of the zinc mediated interruption.
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