Caloric restriction promotes cell survival in a mouse model of normal tension glaucoma.
Caloric restriction promotes cell survival in a mouse model of normal tension glaucoma.
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DOI：
10.1038/srep33950
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发表时间：
2016-09-27
影响因子：
4.6
通讯作者：
Harada T
中科院分区：
文献类型：
--
作者：
Guo X;Kimura A;Azuchi Y;Akiyama G;Noro T;Harada C;Namekata K;Harada T
青光眼的特征在于视网膜神经节细胞（RGC）及其轴突的进行性变性。我们以前报道过，小鼠谷氨酸转运蛋白（EAAC 1或GLAST）的丢失导致RGC变性，这与正常的眼压性青光眼相似，这些动物模型可用于检查潜在的治疗策略。据报道，热量限制可以延长寿命，并对受伤和疾病有潜在的好处。在这里，我们研究了每隔一天禁食（EODF），一种热量限制的形式，对EAAC 1 −/−小鼠的肿瘤病理学的影响。EODF抑制RGC死亡和视网膜变性而不改变眼内压。此外，EODF可改善视力损害，表明EODF的神经保护作用的功能意义。探索了与这种神经保护相关的几种机制。我们发现，EODF上调血液β-羟基丁酸水平，并增加视网膜中的组蛋白乙酰化。此外，它提高了视网膜神经营养因子和过氧化氢酶的mRNA表达水平，而它降低了视网膜中的氧化应激水平。我们的研究结果表明，EODF，一个安全，非侵入性，低成本的治疗，可能是青光眼治疗。
Glaucoma is characterized by progressive degeneration of retinal ganglion cells (RGCs) and their axons. We previously reported that loss of glutamate transporters (EAAC1 or GLAST) in mice leads to RGC degeneration that is similar to normal tension glaucoma and these animal models are useful in examining potential therapeutic strategies. Caloric restriction has been reported to increase longevity and has potential benefits in injury and disease. Here we investigated the effects of every-other-day fasting (EODF), a form of caloric restriction, on glaucomatous pathology in EAAC1−/− mice. EODF suppressed RGC death and retinal degeneration without altering intraocular pressure. Moreover, visual impairment was ameliorated with EODF, indicating the functional significance of the neuroprotective effect of EODF. Several mechanisms associated with this neuroprotection were explored. We found that EODF upregulated blood β-hydroxybutyrate levels and increased histone acetylation in the retina. Furthermore, it elevated retinal mRNA expression levels of neurotrophic factors and catalase, whereas it decreased oxidative stress levels in the retina. Our findings suggest that EODF, a safe, non-invasive, and low-cost treatment, may be available for glaucoma therapy.
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