Tonicity response element binding protein associated with neuronal cell death in the experimental diabetic retinopathy

AIM: To study the contribution of tonicity response element binding protein(Ton EBP) in retinal ganglion cell(RGC) death of diabetic retinopathy(DR).METHODS: Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin(STZ). Control mice received vehicle(phosphate-buffered saline). All mice were killed 2mo after injections, and the extent of cell death and the protein expression levels of Ton EBP and aldose reductase(AR) were examined.RESULTS: The Ton EBP and AR protein levels and the death of RGC were significantly increased in the retinas of diabetic mice compared with controls 2mo after the induction of diabetes. Terminal deoxynucleotidyl transferase(Td T)-mediated d UTP nick end labeling(TUNEL)-positive signals co-localized with Ton EBP immunoreactive RGC. These changes were increased in the diabetic retinas compared with controls.CONCLUSION: The present data show that AR and Ton EBP are upregulated in the DR and Ton EBP may contribute to apoptosis of RGC in the DR.

Aralia elata inhibits neurodegeneration by downregulating O-GlcNAcylation of NF-κB in diabetic mice

AIM： To investigate the role of O-GIcNAcylation of nuclear factor-kappa B （NF-KB） in retinal ganglion cell （RGC） death and analysedthe effect of Aralia elata （AE） on neurodegen- eration in diabetic mice. METHODS： C57BL/6mice with streptozotocin-induced diabetes were fed daily with AE extract or control （CTL） diet at the onset of diabetes mellitus （DM）. Two months af- tar injection of streptozotocin or saline, the degree of cell death and the expression of O-GIcNAc transferase （OGT）, N-acetyl-b-D-glucosaminidase （OGA）, O-GIcNAcylated pro- teins, and O-GIcNAcylation of NF-KB were examined. RESULTS： AE did not affect the metabolic status of diabetic mice. The decrease in the inner retinal thickness （P〈0.001 vs CTL, P〈0.01 vs DM） and increases in RGCs with terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling （P〈0.001 vs CTL, P〈0.0001 vs DM）, glial activation, and active caspase-3 （P〈0.0001 vs CTL, P〈0.0001 vs DM） were blocked in diabetic retinas of AE extract-fed mice. Expression levels of protein O-GIcNAcylation and OGT were increased in diabetic retinas （P〈0.0001 vs CTL）, and the level of O-GIcNAcylation of the NF-KB p65 subunit was higher in diabetic retinas than in controls （P〈0.0001 vs CTL）. AE extract downregulated O-GIcNAcylation of NF-KB and prevented neurodegeneration induced by hyperglycemia （P〈0.0001 vs DM）. CONCLUSION： O-GIcNAcylation of NF-KB is concerned in neuronal degeneration and that AE prevents diabetes-in- duced RGC apoptosis via downregulation of NF-KB O-GI- cNAcylation. Hence, O-GIcNAcylation may be a new object for the treatment of DR, and AE may have therapeutic pos- sibility to prevent diabetes-induced neurodegeneration.