microRNA-26a-5p Prevents Retinal Neuronal Cell Death in Diabetic Mice by Targeting PTEN.

AIM: To explore the role of microRNA-26a-5p (miR-26a) in early diabetic retinal neuronal cell death and reveal the underlying mechanism(s). METHODS: A streptozotocin (STZ)-induced diabetic mouse model was established using C57BL/6 J mice. Control or miR-26a mimic was intravitreally injected. Hematoxylin-eosin (H&E) and transmission electron microscopy (TEM) were used to observe the morphologic alterations in the retinal structure and ultrastructure, respectively. The expression of miR-26a and phosphatase and tensin homolog (PTEN) was assayed using qRT-PCR and western blotting, respectively. An immunofluorescence assay was used to investigate the distribution of PTEN expression in the retina. The expression of glial fibrillary acidic protein (GFAP) was measured to identify glial cell activation. The mRNA levels of IL-1ß, NF-κB, and VEGF were examined to assess diabetic retinal inflammation. RESULTS: miR-26a expression was decreased in retinal tissues of diabetic mice, and injection of miR-26a mimic restored the miR-26a level. Diabetic mice had significantly reduced neuroretinal thickness and ganglion cell number; miR-26a mimic delayed the thinning of neuroretinal layers and the loss of ganglion numbers. TEM showed damaged ultrastructure of retinal ganglions in diabetic mice, while miR-26a mitigated the damages. PTEN expression was increased mainly in the inner and outer nuclear layer of the retina in diabetic mice; miR-26a mimics lowered PTEN expression. GFAP, IL-1ß, NF-κB, and VEGF expression were significantly increased in the diabetic mice, and intravitreal delivery of miR-26a resulted in a down-regulated expression of these factors. CONCLUSION: miR-26a can protect against retinal neuronal impairment in diabetic mice by down-regulating PTEN, highlighting the potential of miR-26a as a target for DR treatment.

Comparison of Conbercept with Ranibizumab for the treatment efficiency of macular edema:a meta-analysis / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To study the clinical effect of Conbercept and Ranibizumab for macular edema ( ME ) with meta -analysis.·METHODS:We searched Pubmed, EMBASE, Cochrane Library Central Register of Controlled Trials ( CENTRAL) , Google scholar, ClinicalTrials. gov, CNKI, VIP and wanfang database for studies which published between January 12012 and July 12017, on the comparison of conbercept with ranibizumab for the clinical effect of secondary macular edema. The primary endpoints were visual acuity ( VA ) and central macular thickness in this study to assess the efficiency of the drugs. Review Manager 5. 3 and Stata 12. 0 were used for data analysis with the pooled odds ratios (OR), mean difference and 95% confidence interval ( CI) .·RESULTS: Eleven RCTs involving 812 patients met inclusion criteria and included in this meta-analysis, including 414 eyes in conbercept group and 398 eyes in ranibizumab group. Macular edema in this study were secondary to age-related macular degeneration, diabetic retinopathy and retinal vein occlusion. No significant differences in improvement of vision acuity(P=0. 09) or reduction of CMT (P>0. 05) were noted at the end of 3mo between two groups. Compared to ranibizumab, conbercept showed a better effectiveness in macular edema alleviation in the end of 6mo in the present study (OR=-58. 50, 95%CI: -108. 04 to -8. 95;P=0. 02).· CONCLUSION: Despite evidence from the meta -analysis of the RCTs suggesting a strong difference of the effectiveness for macular edema between conbercept and ranibizumab, more clinical trials are still needed to confirm our results because of the heterogeneity in the collected data.

The Red Nucleus Interleukin-6 Participates in the Maintenance of Neuropathic Pain Induced by Spared Nerve Injury.

Previous studies have demonstrated that the red nucleus (RN) is involved in the regulation of neuropathic pain and plays both facilitated and inhibitory roles through different cytokines. Here, we aim to investigate the expression changes and roles of interleukin-6 (IL-6), a pleiotropic cytokine, as well as its receptor (IL-6R) in the RN of rats with neuropathic pain induced by spared nerve injury (SNI). Immunohistochemistry indicated that IL-6 and IL-6R were weakly expressed in the RN of normal rats, and were mainly co-localized with neurons and oligodendrocytes. Following SNI, the expression levels of IL-6 and IL-6R in the RN did not show obvious changes at 1 week and 2 weeks postinjury. However, both of them were significantly increased in the RN contralateral (but not ipsilateral) to the nerve ligation side at 3 weeks postinjury, and co-localized not only with neurons and oligodendrocytes, but also with numerous astrocytes. Injection of different doses of anti-IL-6 antibody (100, 250, 500 ng) into the RN contralateral to the nerve ligation side at 3 weeks postinjury dose-dependently increased the paw withdrawal threshold (PWT) of rats and alleviated SNI-induced mechanical allodynia. Conversely, injection of different doses of recombinant rat IL-6 (5.0, 10, 20 ng) into the unilateral RN of normal rats dose-dependently decreased the PWT of contralateral (but not ipsilateral) hind paw and evoked significant mechanical allodynia, which was similar to SNI-induced neuropathic allodynia. These results further support the conclusion that the RN is involved in the modulation of neuropathic pain, and suggest that IL-6 and IL-6R in the RN play a facilitated role in the later maintenance of SNI-induced neuropathic pain.