Neuroprotective effects of brain-derived neurotrophic factor in eyes with NMDA-induced neuronal death

Brain Res. 2000 Nov 24;884(1--2):59-67. doi: 10.1016/s0006-8993(00)02887-0.


Purpose: To determine if brain-derived neurotrophic factor (BDNF) has a neuroprotective effect against N-methyl-D-aspartate (NMDA)-induced cell death in retina.

Methods: NMDA was injected into the vitreous of rat eyes. NMDA-induced neuronal death was measured by morphometric analyses on cell counts of ganglion cell layer cells and thickness of retinal layers. Also, we conducted additional experiment using retrograde labeling with a fluorescent tracer (Fluoro-Gold) for exact counting of retinal ganglion cells (RGCs). In addition, intravitreal glutamate levels were measured with the use of a high-performance liquid chromatography (HPLC) system.

Results: Morphometric analysis of retinal damage in NMDA-injected eyes showed that BDNF could protect inner retinal cells from glutamate receptor-mediated neuronal death. Also, counts of RGCs labeled with a fluorescent tracer showed that BDNF could protect RGCs from glutamate receptor-mediated neuronal death. Furthermore, measurements of intravitreal glutamate levels indicated an increase in this excitatory amino acid in the vitreous after NMDA injection.

Conclusions: Exogenous BDNF can protect inner retinal cells (possible RGCs and amacrine cells) from NMDA-induced neuronal death. However, increased intravitreal glutamate levels in response to NMDA-mediated neurotoxicity may augment retinal degeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • Cell Count / statistics & numerical data
  • Cell Death / drug effects*
  • Cell Death / physiology
  • Fluorescent Dyes
  • Glutamic Acid / metabolism
  • Male
  • N-Methylaspartate / toxicity*
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / drug therapy*
  • Nerve Degeneration / pathology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Neurotoxins / metabolism
  • Neurotoxins / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Retina / drug effects*
  • Retina / pathology
  • Retina / physiopathology
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology
  • Stilbamidines*
  • Vitreous Body / metabolism


  • 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
  • Brain-Derived Neurotrophic Factor
  • Fluorescent Dyes
  • Neuroprotective Agents
  • Neurotoxins
  • Receptors, N-Methyl-D-Aspartate
  • Stilbamidines
  • Glutamic Acid
  • N-Methylaspartate