Low-Dose-Rate, Low-Dose Irradiation Delays Neurodegeneration in a Model of Retinitis Pigmentosa
Low-Dose-Rate, Low-Dose Irradiation Delays Neurodegeneration in a Model of Retinitis Pigmentosa
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DOI：
10.1016/j.ajpath.2011.09.025
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发表时间：
2012-01-01
影响因子：
6
通讯作者：
Yoshimura, Nagahisa
中科院分区：
文献类型：
--
作者：
Otani, Atsushi;Kojima, Hiroshi;Yoshimura, Nagahisa
辐射兴奋效应的存在是有争议的。迄今为止，已报告了低剂量辐射的若干刺激效应;然而，对神经组织或神经变性的影响仍然未知。在这里，我们表明LD辐射在视网膜色素变性小鼠模型中具有神经保护作用，视网膜色素变性是一种导致失明的遗传性、进行性神经退行性疾病。在视网膜变性小鼠模型中，对眼睛给予不同剂量的LD辐射，并分析其病理和生理效应。低剂量率（LDR）条件下的LD γ辐射可从形态学和功能上挽救感光细胞凋亡。在使用650 mGy辐照和26 mGy/分钟剂量率的条件下观察到最大效果。多轮照射加强了这种神经保护作用。与假手术对照组相比，LDR-LD照射组视网膜中抗氧化基因过氧化物酶-2（Prdx 2）的特征性上调（563%）。使用小干扰RNA施用沉默Prdx 2降低了LDR-LD对光感受器的拯救作用。我们的研究结果首次证明LDR-LD照射对活体动物的神经细胞具有生物学效应。结果支持辐射具有兴奋效应，这种效应可以作为视网膜色素变性和其他进行性神经退行性疾病的一种新的治疗概念，无论涉及的变性机制。(Am J Pathol 2012，180：328 DOI：10.1016/j.ajpath.2011.09.025）
The existence of radiation hormesis is controversial. Several stimulatory effects of low-dose (ID) radiation have been reported to date; however, the effects on neural tissue or neurodegeneration remain unknown. Here, we show that LD radiation has a neuroprotective effect in mouse models of retinitis pigmentosa, a hereditary, progressive neurodegenerative disease that leads to blindness. Various LD radiation doses were administered to the eyes in a retinal degeneration mouse model, and their pathological and physiological effects were analyzed. LD gamma radiation in a low-dose-rate (LDR) condition rescues photoreceptor cell apoptosis both morphologically and functionally. The greatest effect was observed in a condition using 650 mGy irradiation and a 26 mGy/minute dose rate. Multiple rounds of irradiation strengthened this neuroprotective effect. A characteristic up-regulation (563%) of antioxidative gene peroxiredoxin-2 (Prdx2) in the LDR-LD irradiated retina was observed compared to the sham-treated control retina. Silencing the Prdx2 using small-interfering RNA administration reduced the LDR-LD rescue effect on the photoreceptors. Our results demonstrate for the first time that LDR-LD irradiation has a biological effect in neural cells of living animals. The results support that radiation exhibits hormesis, and this effect may be applied as a novel therapeutic concept for retinitis pigmentosa and for other progressive neurodegenerative diseases regardless of the mechanism of degeneration involved. (Am J Pathol 2012, 180:328 DOI: 10.1016/j.ajpath.2011.09.025)