Increased expression of c-Fos, c-Jun and c-Jun N-terminal kinase associated with neuronal cell death in retinas of diabetic patients.
OBJECTIVE
To examine whether c-Fos, phosphorylated c-Jun (p-c-Jun), members of transcriptional factor activator protein 1 (AP-1) family and phosphorylated c-Jun N-terminal kinase (p-JNK) are associated with neuronal degeneration in retinas of diabetic patients.


METHODS
Retinal cryosections from five pairs of normal and five pairs of diabetic human eyes were immunostained for c-Fos, p-c-Jun and p-JNK followed by costaining with Fluoro-Jade B (FJB), a marker for identifying degenerative neurons. Additionally, cells were stained with 4, 6-diamidino-2-phenyl indole (DAPI) to facilitate counting the total number of cells. The number of c-Fos, p-c-Jun and p-JNK positive cells costained with FJB was assessed in the ganglion cell layer (GCL) together with the total number of DAPI-positive cells.


RESULTS
The number of FJB-positive cells in the GCL of diabetic retinas was significantly increased compared to those of non-diabetic retinas. The GCL of diabetic retinas, compared to those of the non-diabetic retinas, showed increased number of c-Fos, p-c-Jun and p-JNK-positive cells that coexisted with FJB-positive signals.


CONCLUSIONS
This study indicates that increased expression of c-Fos, p-c-Jun, members of AP-1 transcriptional factor and p-JNK is associated with neuronal degeneration in the GCL of retinas in diabetic patients.
Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine , Chiba , Japan and.
Toshiyuki
T
Oshitari
Shuichi
S
Yamamoto
Sayon
S
Roy
D000368:Aged; D017209:Apoptosis / Q000502:physiology; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D048055:Mitogen-Activated Protein Kinase 8