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K. T. Tchedre, R. Krishnamoorthy, T. Yorio; Regulation of Calcium Influx in Retinal Ganglion Cells by Sigma-1 Receptor Ligands and Neuroprotection Relevance. Invest. Ophthalmol. Vis. Sci. 2007;48(13):572.
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The purpose of this study was to investigate the effect of sigma-1 receptor ligands on the modulation of the intracellular calcium through N-methyl-d-aspartate (NMDA) receptor and voltage gated calcium L-type calcium channels in endogenously expressed retinal ganglion cell line (RGC-5), sigma-1 receptor overexpressing retinal ganglion (RGC-5), and primary retinal ganglion cell (RGC) cells and its role in neuroprotection.
Western Blot and RT-PCR were used to analyze the expression of sigma-1 receptor in differentiated, undifferentiated, and sigma-1 receptor overexpressing RGC-5 cells. The calcium imaging results have shown that sigma-1 receptor ligand, (+)-N-allylnormetazocine hydrochloride [(+) SKF10047] differentially inhibits the glutamate and KCl induced calcium influx in both types of RGC-5 cells while haloperidol and BD10047 reversed the effect of (+) SKF10047 in RGC-5 cells. KCl induced calcium influx was affected by depletion of calcium from the perfusion buffer. Co-immunoprecipitation was used to show the association between L-type calcium channels and sigma-1 receptors. Whole-cell patch clamp of rat cultured retinal ganglion cells (RGC) demonstrated that sigma-1 receptor ligand (+) SKF10047 inhibits L-type voltage gated calcium channels current.
These results suggest that sigma-1 receptor activation can modulate calcium homeostasis in RGC by regulating calcium signaling. Differential inhibition of calcium influx in retinal ganglion cells by sigma-1 receptor ligands may lead to the use of sigma-1 receptor ligands in clinical studies, and ultimately lead to the development of a new series of neuroprotective agents for the eye.
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