BDNF diminishes caspase-2 but not c-Jun immunoreactivity of neurons in retinal ganglion cell layer after transient ischemia.
OBJECTIVE
Retinal ischemia-reperfusion injury induces apoptosis of retinal neurons. The purpose of this study was to examine the association of c-Jun, caspase-1, -2, and -3 immunoreactivities and neuronal apoptosis in the retinal ganglion cell layer (GCL) and to study the effects of intravitreal brain-derived neurotrophic factor (BDNF) on the expression of these gene products in a rat model of retinal ischemia-reperfusion injury.


METHODS
After 60 minutes of ischemia, eyes were enucleated after 3, 6, 12, 24, and 168 hours of reperfusion. The numbers of c-Jun-, caspase-1-, caspase-2-, caspase-3, and TdT-dUTP terminal nick-end labeling (TUNEL)-positive cells in the GCL were counted. Recombinant human BDNF (5 microg) or vehicle was injected intravitreally immediately after reperfusion. At 6, 24, and 168 hours, the numbers of immunoreactive cells in BDNF- and vehicle-treated groups were compared.


RESULTS
Expression of c-Jun and caspase-2 was found in dying cells in flat-mounted retinas. The numbers of caspase-1- and caspase-3-positive cells were fewer than c-Jun- or caspase-2-positive cells. Cell death in the retinal GCL was suppressed by an intravitreal injection of BDNF. The numbers of TUNEL- and caspase-2-positive cells were lower in the BDNF-treated group at 6 hours after reperfusion (P<0.01). The number of c-Jun-positive cells in the treated retinas was not altered by the treatment.


CONCLUSIONS
Expression of c-Jun and caspase-2 is associated with neuronal cell apoptosis in the GCL. Suppression of caspase-2 expression may explain the neuroprotective effects of BDNF.
Kurokawa
T
T
Department of Ophthalmology, Shinshu University School of Medicine, Matsumoto, Japan.
Katai
N
N
Shibuki
H
H
Kuroiwa
S
S
Kurimoto
Y
Y
Nakayama
C
C
Yoshimura
N
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D053143:Caspase 2; D020169:Caspases / Q000378:metabolism*; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D020287:In Situ Nick-End Labeling; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels
D019208:Brain-Derived Neurotrophic Factor; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D053143:Caspase 2; D020169:Caspases