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Toshiyuki Oshitari, Shuichi Yamamoto, Sayon Roy; Upregulation of activator protein 1 (c-Fos/c-Jun) and c-Jun N-terminal kinase associated with neuronal cell death in retinas of diabetic patients. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2692.
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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.
Retinal cryosections from five normal and five diabetic human eyes obtained from the National Disease Research Interchange in accordance with the provisions of the Declaration of Helsinki for research involving human tissue, were immunostained for c-Fos, p-c-Jun and p-JNK followed by co-staining 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 assessment of the total number of cells. The number of c-Fos, p-c-Jun and p-JNK positive cells co-stained with FJB were counted in the ganglion cell layer (GCL) together wit the total number of DAPI positive cells.
The number of FJB positive cells in the GCL of diabetic retinas were significantly increased compared to those of non-diabetic retinas (273.5±205.9% of control, p=0.0012). Similarly, 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 co-existed with FJB positive signals (205.3±134.2% of control vs. 82.1±74.4% of control, 314.7±144.1% of control vs. 111.8±88.2% of control, 241.2±223.5% of control vs. 100.0±70.6% of control; P=0.0149, P=0.0138, P=0.0276, respectively).
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.
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