Abstract

SA.08.02

Role of Glia in Neuroprotection

Andreas Reichenbach
Paul-Flechsig-Institut für Hirnforschung, Universität Leipzig

Objective: There is now overwhelming experimental evidence for the view that normal function and survival of retinal neurons are crucially dependent on biochemical and physiological interactions with Müller glial cells. Recent data suggest that also the biomechanical properties of glial cells may be important for neurite growth during neuronal plasticity and regeneration, and perhaps for other neuronal functions.
Methods: To test this hypothesis, we used atomic force microscopy and the ‘optical stretcher’ to assess the viscoelastic properties of live Müller cells isolated from rodent retinae. In particular, we studied Müller cells from GFAP-vimentin double-KO mice, control mice, and mice which had been subjected to ocular ischemia-reperfusion. Furthermore, a specific experimental setup was generated to monitor Ca2+ rises in Müller cells after mechanical stimulation of the isolated retina.
Results: We show that (i) normal glial cells are softer than neurons and display the features of soft elastic springs, (2) Müller cells devoid of intermediate filaments are even softer than normal cells, and (iii) reactive Müller cells with enhanced content of intermediate filaments are stiffer than normal cells. Thus, indeed gliotic scars may interfere with regenerative growth of neurites. Furthermore, we found that Müller cells ‘sense’ mechanical stress applied to the retina, and respond by intracellular Ca2+ rises. This triggers the expression of early immediate genes, and finally of bFGF in Müller cells which may be released as a neuroprotective factor.
Conclusions: Biomechanical properties of glial cells indeed may play an important role in neuronal degeneration and regeneration. Reactive Müller cells may both impair and support neuronal regeneration. It remains to be established how the anti-regenerative responses may be inhibited, and the pro-regenerative responses may be stimulated, in order to develop novel therapeutic approaches.

Copyright: 2009 Porstmann Kongresse GmbH. All rights reserved. Impressum, Disclaimer.