Abstract

DMP 543, a functional analog of linopirdine, acts as a potassium channel blocker in neuronal cells. In the retina, this lab has previously shown that DMP 543 stimulates an increase in the release of the neurotransmitter acetylcholine (ACh). Using a mixed retinal cell culture, it was observed that DMP 543 can increase retinal cell survival. Additionally, using positive allosteric modulators (PAMs) and an antagonist to different nicotinic acetylcholine receptors (nAChRs) on retinal ganglion cells (RGCs, the targets of degeneration in glaucoma), it was demonstrated that both α7 and α4β2 nAChRs play a role in the neuroprotective response to the increased levels of ACh released. Finally, within an intact retina, confocal microscopy was used to visualize activation of intracellular calcium dynamics in both the amacrine cell layer (location of ACh-releasing cells) and the retinal ganglion cell layer in response to application of increasing DMP 543 concentrations.