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-GlcNAcylation of nuclear factor-kappa B(NF-κB) in retinal ganglion cell(RGC) death and analysedthe effect of Aralia elata(AE) on neurodegeneration 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 after injection of streptozotocin or saline,the degree of cell death and the expression of O-GlcN Ac transferase(OGT),N-acetyl-b-D-glucosaminidase(OGA),O-GlcN Acylated proteins,and O-GlcNAcylation of NF-κB 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 d UTP 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-Glc NAcylation and OGT were increased in diabetic retinas(P<0.0001 vs CTL),and the level of O-GlcNAcylation of the NF-κB p65 subunit was higher in diabetic retinas than in controls(P<0.0001 vs CTL). AE extract downregulated O-GlcNAcylation of NF-κB and prevented neurodegeneration induced by hyperglycemia(P<0.0001 vs DM).CONCLUSION: O-GlcNAcylation of NF-κB is concerned in neuronal degeneration and that AE prevents diabetes-induced RGC apoptosis via downregulation of NF-κB O-GlcNAcylation. Hence,O-GlcNAcylation may be a new object for the treatment of DR,and AE may have therapeutic possibility to prevent diabetes-induced neurodegeneration.

Comparison of anterior segment optical coherence tomography findings in acanthamoeba keratitis and herpetic epithelial keratitis

This study is to investigate the characteristic features of Acanthamoeba keratitis(AK) that differentiating it from herpetic epithelial keratitis(HEK) using anterior segment optical coherence tomography(AS-OCT). Medical records of three eyes of each AK and herpetic keratitis who had AS-OCT examination were reviewed in this study. Slitlamp biomicroscopy and AS-OCT was performed on the initial visit and on every follow-up visits in all patients. In all three AK cases, reflective bands in the corneal stroma that correspond to the area of radial keratoneuritis were observed. The depth of the reflective bands varied in each case. After AK treatment, slit-lamp biomicroscopy confirmed that radial keratoneuritis had resolved and AS-OCT confirmed that reflective bands in the corneal stroma had also disappeared in all patients. Unlike the AS-OCT results found in AK, highly reflective HEK lesions were observed only in the subepithelial area, not in the stroma. AS-OCT seems to be helpful analyzing the specific depth of the lesion which enables to distinguish AK from HEK.