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Up-regulation of brain-derived neurotrophic factor by application of fibroblast growth factor-2 to the cut optic nerve is important for long-term survival of retinal ganglion cells

Authors

  • Rosa E. Blanco,

    Corresponding author
    1. Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, Old San Juan, Puerto Rico
    2. Department of Anatomy and Neurobiology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico
    • Institute of Neurobiology, 201 Boulevard del Valle, San Juan, Puerto Rico 00901
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  • Ileana Soto,

    1. Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, Old San Juan, Puerto Rico
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  • Mildred Duprey-Díaz,

    1. Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, Old San Juan, Puerto Rico
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  • Jonathan M. Blagburn

    1. Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, Old San Juan, Puerto Rico
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Abstract

Application of basic fibroblast growth factor (FGF-2) to the optic nerve after axotomy promotes the survival of retinal ganglion cells (RGCs) in the frog Rana pipiens and results in a rapid up-regulation of brain-derived neurotrophic factor (BDNF) and TrkB synthesis by the RGCs. Here we investigate whether this up-regulation is maintained over the long term and whether it is required for FGF-2's survival effect. At 6 weeks after axotomy and FGF-2 treatment, we found more RGCs immunopositive for BDNF protein and higher intensity of BDNF and TrkB immunostaining, accompanied by increases in BDNF and TrkB mRNA in RGCs. Application of fluorescently labeled siRNA targeted against BDNF to the cut RGC axons showed that it was transported to the cell bodies. Axonal siRNA treatment eliminated the increases in BDNF immunostaining and mRNA that were induced by FGF-2 and had no effect on TrkB mRNA. This reduction in BDNF synthesis by siRNA greatly reduced the long-term survival effect of FGF-2 on RGCs. This, taken together with previous results, suggests that, although FGF-2 may initially activate survival pathways via ERK signaling, its main long-term survival effects are mediated via its up-regulation of BDNF synthesis by the RGCs. © 2008 Wiley-Liss, Inc.

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