Doheny Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Invest Ophthalmol Vis Sci. 2012 Feb 13;53(2):704-11. doi: 10.1167/iovs.11-7408. Print 2012 Feb.
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.
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.
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.
Neuroglobin overexpression plays a neuroprotective role against retinal ischemia reperfusion injury due to decreasing of mitochondrial oxidative stress-mediated apoptosis.
神经球蛋白（Ngb）是一种脊椎动物球蛋白，主要在视网膜和大脑中表达。为了探讨 Ngb 在缺血再灌注（IR）期间视网膜神经保护中的作用，作者通过使用 Ngb 转基因（Ngb-Tg）小鼠研究了 Ngb 在体内视网膜中的过表达作用。
通过在前房内插管并短暂升高眼内压 60 分钟，在 Ngb 过表达的 Ngb-Tg 小鼠和野生型（WT）小鼠中诱导视网膜 IR。在再灌注第 7 天，作者评估了非缺血性对照以及缺血性小鼠中非缺血性对照以及缺血性小鼠中的 Ngb mRNA 和蛋白表达及其对视网膜组织学、线粒体氧化应激和细胞凋亡的影响，使用形态计量学和免疫组织化学、定量 PCR 分析和 Western blot 技术。
没有缺血的 Ngb-Tg 小鼠的 Ngb mRNA 表达水平比 WT 对照小鼠高 11.3 倍（SE ± 0.457，P < 0.05），并且这种 Ngb 蛋白的过表达定位于节细胞、外丛状层和内丛状层以及光感受器内节的线粒体。与 WT 相比，IR 中的 Ngb-Tg 小鼠的线粒体 DNA 损伤减少，与 Ngb 过表达相关。与 WT 相比，IR 中的 Ngb-Tg 小鼠的视网膜厚度明显保留，激活的 caspase 3 蛋白表达和细胞凋亡明显减少。
神经球蛋白过表达通过减少线粒体氧化应激介导的细胞凋亡，对视网膜缺血再灌注损伤发挥神经保护作用。
