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Jun Kaneko, Michiko Mandai, Masayo Takahashi; Light-evoked Response Recordings from Degenerating Mouse Retina: Effect of Valproic Acid Application on Spontaneous Activity. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5092.
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Inherited retinal degeneration such as retinitis pigmentosa (RP) results in photoreceptor death and functional blindness. Consequently, retinal circuit remodeling occurs accompanied by increased spontaneous spiking activity of the retina’s main output cells, the retinal ganglion cells (RGC). Understanding the impact of photoreceptor loss to the retinal structure and function is prerequisite for approaches aimed at restoring vision in retinal degeneration. The aim of this study is to characterize the physiological properties of RGC in degenerating retina, including light-evoked response, by electrophysiological analyses and pharmacological experiments.
Rd1 mouse, an animal model of retinitis pigmentosa, was used in this study. The retinas from dark-adapted mice were prepared for the in vitro electrophysiological study. For Microelectrode array (MEA) recording, a total 8x8 electrodes in 1.2mm square were positioned against each retina, and electrical responses were recorded from the cells in ganglion cell layer on each electrode with bath application of pharmacological substances and light stimulation. Conventional whole cell patch-clamp analysis was performed as well to characterize the physiological properties of RGC in rd1 mouse retinas.
Rd1 mice retina showed spontaneous bursts of ganglion cell action potentials with and without light stimulation. Valproic Acid (VPA) which is known as a GABA transaminase inhibitor inhibited the spontaneous spikes of RGC and revealed remaining light-evoked responses clearly. After washing out VPA, the spontaneous spikes recovered immediately. In addition, Vigabatrin, one of the GABA transaminase inhibitors, inhibited the spontaneous spikes as well. Furthermore, TPMPA, a GABAc receptor antagonist, partially recovered the spontaneous activity in the presence of VPA.
We could detect remaining light-evoked responses reliably from RGC in degenerating retina by inhibiting spontaneous activity of degenerating retina with VPA. Our results indicate alteration of GABAergic inputs may be involved in the spontaneous activity of RGC in degenerating retina.
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