Expression of Glial Fibrillary Acidic Protein and Glutamine Synthetase by Mu ¨ ller Cells After Optic Nerve Damage and Intravitreal Application of Brain-Derived Neurotrophic Factor HAO CHEN 1 AND ARTHUR J. WEBER 2 * 1 Department of Pharmacology, University of Tennessee at Memphis, Memphis, Tennessee 2 Department of Physiology and the Neuroscience Program, Michigan State University, East Lansing, Michigan KEY WORDS retina; degeneration; neurotrophin; immunocytochemistry; ganglion cells ABSTRACT Mu ¨ ller glia play an important role in maintaining retinal homeostasis, and brain-derived neurotrophic factor (BDNF) has proven to be an effective retinal ganglion cell (RGC) neuroprotectant following optic nerve injury. The goal of these studies was to investigate the relation between optic nerve injury and Mu ¨ ller cell activation, and to determine the extent to which BDNF affects the injury response of Mu ¨ ller cells. Using immunocytochemistry and Western blot analysis, temporal changes in the expression of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) were examined in rats after optic nerve crush alone, or in conjunction with an intra- vitreal injection of BDNF (5 g). GFAP protein levels were normal at 1 day post-crush, but increased 9-fold by day 3 and remained elevated over the 2-week period studied. Mu ¨ ller cell GS expression remained stable after optic nerve crush, but the protein showed a transient shift in its cellular distribution; during the initial 24-h period post-crush the GS protein appeared to translocate from the cell body to the inner and outer glial processes, and particularly to the basal endfeet located in the ganglion cell layer. BDNF alone, or in combination with optic nerve crush, did not have a significant effect on the expression of either GFAP or GS compared with the normal retina, or after optic nerve crush alone, respectively. The data indicate that although BDNF is a potent neuroprotectant in the vertebrate retina, it does not appear to have a significant influence on Mu ¨ ller cell expression of either GS or GFAP in response to optic nerve injury. GLIA 38: 115–125, 2002. © 2002 Wiley-Liss, Inc. INTRODUCTION The mammalian CNS contains two general types of cells: neurons and glia. While neurons provide the ba- sis for complex electrophysiological activities, the pri- mary role of glia is support. However, in addition to providing structural support to the nervous system, glia also have been shown to play an important role in neurotransmitter metabolism, to serve as modulators of synaptic transmission, and to help maintain a ho- meostatic environment for neurons (see Kettenmann, 1996, for review). Grant sponsor: National Institutes of Health; Grant number: EY11159; Grant sponsor: Strategic Partnership Fund of Michigan State University. *Correspondence to: Arthur J. Weber, Department of Physiology, B-512 West Fee Hall, Michigan State University, East Lansing, MI 48824. E-mail: weberar@msu.edu Received 25 July 2001; Accepted 14 January 2002 DOI 10.1002/glia.10061 Published online 00 Month 2002 in Wiley InterScience (www.interscience. wiley.com). GLIA 38:115–125 (2002) © 2002 Wiley-Liss, Inc.