Aralia elata Prevents Neuronal Death by Downregulating Tonicity Response Element Binding Protein in Diabetic Retinopathy

BACKGROUND/AIMS: The present study addresses the role of tonicity response element binding protein (TonEBP) in retinal ganglion cell (RGC) death in diabetic retinopathy and the impact of Aralia elata extract on the TonEBP/RGC interaction. METHODS: Diabetes was induced in C57BL/6 mice by intraperitoneal injection of streptozotocin (STZ). Control mice received phosphate-buffered saline. After five injections of STZ or saline buffer, A. elata extract was administered by daily oral tube feeding for 7 weeks. All mice were killed at 2 months after the last injection of STZ or saline and the extent of cell death together with the protein expression levels of TonEBP, aldose reductase (AR) and nuclear factor-kappa B (NF-κB) were examined. RESULTS: Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive signals were colocalized with TonEBP-immunoreactive RGCs. The apoptotic cell death of RGCs and the expression levels of TonEBP, AR and NF-κB were significantly increased in the retinas of diabetic mice compared with controls at 2 months after the induction of diabetes. However, these changes were effectively blocked by the administration of A. elata extract. CONCLUSIONS: These results indicate that A. elata prevents diabetes-induced RGC apoptosis and downregulates TonEBP expression. Therefore, A. elata extract may have therapeutic potential to prevent diabetes-induced retinal neurodegeneration in diabetic retinopathy.