Project Details
Projekt
Calcium and anatomical imaging of the live mouse retina during EAE: insights into the cascade of neurodegeneration
Applicants
Dr. Sarah Fairless; Professor Dr. Frank Winkler
Subject Area
Molecular and Cellular Neurology and Neuropathology
Term
from 2015 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 262890264
Inflammation of the CNS, including the optic system, is closely associated with neurodegeneration. However, the sequence and causality of the single steps that ultimately lead to neuronal death are not well understood, including the role of calcium fluctuations in this process. This is partly due to the lack of adequate animal models that allow the study of the dynamics of neuronal viability in relation to crucial environmental factors and dynamic calcium changes during inflammation. Using a novel animal model of two-photon intravital microscopy of the mouse retina, we will monitor in high resolution the progression of retinal ganglion cell (RGC) degeneration during autoimmune optic neuritis, together with changes in microglial localization and activation, T cell interactions, and microvascular permeability.Through selective loading of RGCs with intracellular calcium indicators, and novel genetically encoded calcium indicators that partly allow ratiomeric calcium measurements, changes in calcium fluctuations will be monitored in vivo throughout the progression of the disease.Furthermore, intercellular calcium waves of glial cells will be recorded and analyzed, and their impact on subsequent neurodegeneration determined. Thus, the ultimate aim is to clarify the temporal interplay of calcium fluctuations in central retinal cell types, and its connection with other cellular and physiological factors, preceding or following neurodegeneration in the retina. From this we expect to obtain insight into neuroprotective strategies, particularly regarding the optimal time point and modality of interference with CNS cells types, and their cellular calcium homeostasis. Using the knowledge gained from these experiments, appropriate therapeutic approaches will then be assessed.
DFG Programme
Research Units
