Increased Expression of c-Fos, c-Jun and c-Jun N-Terminal Kinase Associated with Neuronal Cell Death in Retinas of Diabetic Patients

Abstract

Purpose: 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.

Materials and 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.

• c-Fos
• c-Jun
• c-Jun N-terminal kinase
• diabetic retinopathy
• neuronal degeneration