Frank W. Pfrieger

Biography

We are interested in neuron-glia interactions in the mammalian central nervous system. We focus on the retina, where we study the functions of Müller cells, radial glia-like cells that span across the retina and touch all retinal neurons. Currently, we are working on two projects. First, we study the metabolism of cholesterol in the retina based on our working hypotheses are that retinal ganglion cells depend on the supply by Müller cells and that a breakdown of the cholesterol delivery causes their degeneration. We are testing these hypotheses in vitro using cultures of highly purified ganglion cells and in vivo using mice with a spontaneous mutation in the NPC1 protein, an endosomal/lysosomal component that mediates the intracellular redistribution of externally acquired cholesterol. Mutations in the Npc1 gene cause Niemann-Pick type C disease, a rare and fatal lysosomal storage disorder, which is characterized by visceral and neurologic symptoms. Second, we address the physiologic relevance of "gliotransmission", which postulates that glial cells release molecules like glutamate via calcium-dependent vesicular release. To this end, we have developed new transgenic mice for temporally controlled and cell-specific block of exocytosis by targeted expression of a clostridial neurotoxin. We are using these mice to test whether inhibition of exocytosis in Müller cells affects retinal structure and function in vivo.

Research Interest

Glia-Synapse Interactions