Can Drugs for Alzheimer\u27s Disease Protect Retinal Cells in a \u27Mixed\u27 Culture System?

Glaucoma, a neurodegenerative disease, is a leading cause of blindness. It is known that activation of α7 nicotinic ACh receptors (nAChRs) on retinal ganglion cells (RGCs) can provide neuroprotection. Theoretically, if one could increase the amount of ACh released, then more nAChRs should be activated and more neuroprotection observed. DMP 543 was originally developed to treat Alzheimer’s disease by increasing the release of ACh in the brain. Previous S^3 work has shown that DMP increases the release of ACh from a pig eye-cup preparation. For this S^3 project, we wanted to determine if a ‘mixed’ retinal cell culture (including cholinergic cells and RGCs) could indirectly detect the release of ACh by increased cell survival. Using this ‘mixed’ culture, we have observed a dose-dependent effect of DMP on cell survival. Currently, we are testing the effects of a selective α7 antagonist and modulator to confirm a direct effect and determine the extent of basal ACh release in our system