Neuroglobin Protection in Retinal Ischemia
Neuroglobin Protection in Retinal Ischemia
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DOI：
10.1167/iovs.11-7408
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发表时间：
2012-02-01
影响因子：
4.4
通讯作者：
Rao, Narsing A.
中科院分区：
文献类型：
--
作者：
Chan, Anita S. Y.;Saraswathy, Sindhu;Rao, Narsing A.
目的。脑红蛋白(NGB)是一种脊椎动物珠蛋白，主要在视网膜和大脑中表达。为探讨NGB在视网膜缺血再灌注(IR)时的神经保护作用，采用NGB转基因小鼠(NGB-TG)观察了NGB在视网膜中的过表达作用。方法将NGB高表达的NGB-TG小鼠和野生型(WT)小鼠前房置管，一过性升高眼压60min，诱导视网膜IR。结果：未发生缺血的NGB-TG小鼠NGB基因的过度表达是WT对照组小鼠的11.3倍(SE+/-0.457，P<；0.05)，这种过度表达定位于神经节细胞的线粒体、内外网状层和光感受器内节段。这种NGB的过度表达与与WT相比，IR的NGB-TG小鼠的线粒体DNA损伤减少有关。与WT小鼠相比，NGB-TG小鼠视网膜厚度明显保留，活化的caspase-3蛋白表达明显减少，细胞凋亡明显减少。结论：脑红蛋白过度表达对视网膜缺血再灌注损伤具有神经保护作用，其机制可能与减少线粒体氧化应激介导的细胞凋亡有关。(投资眼科VS科学。2012年；53：704-711)doi：10.1167/iovs.11-7408
PURPOSE. Neuroglobin (Ngb) is a vertebrate globin that is predominantly expressed in the retina and brain. To explore the role of Ngb in retinal neuroprotection during ischemia reperfusion (IR), the authors examined the effect of Ngb overexpression in the retina in vivo by using Ngb-transgenic (Ngb-Tg) mice.METHODS. Retinal IR was induced in Ngb overexpressing Ngb-Tg mice and wild type (WT) mice by cannulating the anterior chamber and transiently elevating the IOP for 60 minutes. After Day 7 of reperfusion, the authors evaluated Ngb mRNA and protein expression in nonischemic control as well as ischemic mice and its effect on retinal histology, mitochondrial oxidative stress, and apoptosis, using morphometry and immunohistochemistry, quantitative PCR analysis and Western blot techniques.RESULTS. Ngb-Tg mice without ischemia overexpress Ngb mRNA 11.3-fold (SE +/- 0.457, P < 0.05) higher than WT control mice, and this overexpression of Ngb protein was localized to the mitochondria of the ganglion cells, outer and inner plexiform layers, and photoreceptor inner segments. This overexpression of Ngb is associated with decreased mitochondrial DNA damage in Ngb-Tg mice with IR in comparison with WT. Ngb-Tg mice with IR also revealed significant preservation of retinal thickness, significantly less activated caspase 3 protein expression, and apoptosis in comparison with WT mice.CONCLUSIONS. Neuroglobin overexpression plays a neuroprotective role against retinal ischemia reperfusion injury due to decreasing of mitochondrial oxidative stress-mediated apoptosis. (Invest Ophthalmol Vis Sci. 2012;53:704-711) DOI:10.1167/iovs.11-7408