Toxic Aß oligomers attach to the membranes of different types of neuronal and neurosensory cells, such as retinal ganglion cells (RGCs), retinal pigment epithelium (RPE) cells and hippocampal neurons, causing them to lose their electrical membrane potential and eventually killing them. This is common to various neurodegenerative diseases such as glaucoma, AMD or AD.
Results from a patch-clamp experiment in RGCs from mice cultivated for 5-7 days demonstrate the potential for being measured as indicator for the toxic effect of increasing concentrations of Aβ oligomers. A concentration of only 44 nmol/l Aβ kills 50% of the cells in culture (Fig. 3).
In cell culture experiments, a moderate concentration (50 nmol/l) of Aβ was administered to the cultures of the different cell types shown (Fig. 4, grey bars). This reduced the membrane potential (or a similar electrophysiological parameter like long term potentiation of fEPSPs) significantly but did not kill the cells immediately. The three different cells types shown represent the main cells affected in neurodegenerative diseases: glaucoma (retinal ganglion cells), dry AMD (retinal epithelium cells), and AD (hippocampal neurons). As seen in each case, the addition of GAL-101 counteracted the toxic effect significantly.