A possible connection between Glaucoma and Alzheimer's Disease
Live imaging experiments in the frog optic nerve are proposed to determine the interdependence of Abeta and mitochondria release from axons.
One aim proposes to examine whether axon-derived mitochondria debris and Abeta are cleared together, be it through glymphatic channels or by myeloid cells, and to determine whether perturbing mitophagy, which increases axonal mitochondria release, also leads to an increase in Abeta release. That is, this aim will determine the degree to which mitochondria and Abeta releases are correlated and whether perturbing mitochondria release affects Abeta release as well. The second aim then tries to determine the converse, namely whether Abeta release might functionally affect mitochondria release.
The most innovative aspect is the concept that Abeta accumulation outside of cells might be due to the unusual process of axons shedding mitochondria. Besides this conceptual innovation, there are also innovative live imaging approaches and the use of a frog system to address questions of direct relevance to both Glaucoma and Alzheimer's Disease.
If our hypothesis is supported by proposed experiments, more conventional mouse-based experiments typical of Glaucoma or Alzheimer's Disease research would be warranted and quite likely fundable by more conventional funding mechanisms. If the hypothesis were ultimately correct in whole or large part, it would provide a very different understanding of what might be at the root of pathology in both Glaucoma and Alzheimer's disease, and as such, would open very novel interventional strategies that are not currently being contemplated.