Neuroprotective effects of brain-derived neurotrophic factor in eyes with NMDA-induced neuronal death.
OBJECTIVE
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.
Kido
N
N
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Tanihara
H
H
Honjo
M
M
Inatani
M
M
Tatsuno
T
T
Nakayama
C
C
Honda
Y
Y
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology*; D002452:Cell Count / Q000706:statistics & numerical data; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D005456:Fluorescent Dyes; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013266:Stilbamidines; D014822:Vitreous Body / Q000378:metabolism
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D019208:Brain-Derived Neurotrophic Factor; D005456:Fluorescent Dyes; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D013266:Stilbamidines; D018698:Glutamic Acid; D016202:N-Methylaspartate