Research Projects
The mammalian central nervous system consists of neurons and several types of glial cells including astrocytes, oligodendrocytes and microglia, which have distinct morphologies and functions. We focus on the retina because of its layered structure and experimental accessibility, and we study the roles of Müller cells, radial glia-like cells that span across the retina and touch all retinal neurons. Concretely, we are working on two projects:
1. Role of glial cells in neuronal cholesterol homeostasis.
Based on our previous work, we are studying the metabolism of cholesterol in the retina. Our working hypotheses are that retinal ganglion cells cannot produce cholesterol efficiently and 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. This endosomal/lysosomal protein mediates the intracellular redistribution of externally acquired cholesterol. Mutations in human NPC1 cause an ultimately fatal lysosomal storage disorder named Niemann-Pick type C disease, which is characterized by visceral and neurologic symptoms.
2. Physiologic relevance of gliotransmission.
The development, function and pathology of the brain depend on neuron-glia interactions. These interactions are mediated in part by molecules that are secreted by glial cells. There is evidence, mainly from in vitro studies, that glial release happens via calcium-dependent vesicular release (i.e. exocytosis), a process that has been termed - somewhat provocatively - gliotransmission. To address whether calcium-dependent exocytosis from glial cells in vivo has a physiologic function, we developed new transgenic mice for temporally controlled and cell-specific block of exocytosis. We are now testing whether inhibition of exocytosis in Müller cells affects retinal structure and function in vivo using a wide range of experimental approaches.
Last Update 5-Aug-2011 by FW Pfrieger. Paintings by Paul Cezanne "La Montagne Sainte-Victoire", 1885-1895, The Barnes Foundation, Merion, Pennsylvania and "Le Mont Sainte-Victoire vu des Lauves", 1904-06, Venturi 1529, Kunstmuseum, Basel. Scans by Mark Harden