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Gianluca Tosini, ilaria Piano, Glaudia Gargini, Kenkichi Baba; Heteromeric MT1/MT2 Melatonin Receptors Signal Via PKC-ζ in Mouse Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2017;58(8):213.
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© ARVO (1962-2015); The Authors (2016-present)
Melatonin plays an important role in the modulation of retinal function and previous studies have also shown that the action of melatonin on photoreceptor is mediated by melatonin receptors heterodimers. Furthermore, it has been reported that the melatonin-induced increase in the amplitude of a- and b-wave is significantly blunted by inhibition of PKC. Previous work has also shown that PKCζ is present in the photoreceptors, thus suggesting that PCKz may be involved in the modulation of melatonin signaling in the photoreceptors.
To determine the role PKC-ζ in the modulation of the melatonin effect on the scotopic ERG mice were injected with melatonin and with specific inhibitors of different PKC isoforms. PKCζ knock-out (KO) mice were also used in this study. PKCζ activation in the photoreceptors following melatonin injection was also investigated with immunocytochemistry.
Inhibition of PKCζ by PKCζ-pseudosubstrate inhibitor (20 μM) significantly reduced the melatonin-induced increase in the amplitude of the a- and b-wave (Two-way ANOVA, P < 0.01). To further investigate the role of different PKCs in the modulation of the ERGs we tested whether intra-vitreal injection of Enzastaurin (a potent inhibitor of PCKα, PKCβ, PKCγ and PKCε) has any effect on the melatonin-induced increase in the a- and b-wave of the scotopic ERGs. Enzastaurin (100 μM) did not prevent the melatonin-induced increase in the amplitude of the a-wave (Two-way ANOVA, P > 0.01) thus suggesting that PKCα, PCKβ, PKCγand PKCε may be not involved in this phenomenon. Finally our data indicated in mice lacking PKCζ melatonin injection failed to increase the amplitude of the a- and b-waves of the scotopic ERGs. An increase in PKCz phosphorylation in the photoreceptors was also observed by immunocytochemistry.
Our data indicate that MT1/MT2 signaling does indeed use PKCζ pathway to increase the amplitude of the a- and b-wave of the ERG. We are now investigating the effects of PKC-ζ removal on photoreceptor physiology.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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