Interleukin-1 attenuates normal tension glaucoma-like retinal degeneration in EAAC1-deficient mice
Interleukin-1 attenuates normal tension glaucoma-like retinal degeneration in EAAC1-deficient mice
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DOI：
10.1016/j.neulet.2009.09.029
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发表时间：
2009-11-13
影响因子：
2.5
通讯作者：
Harada, Takayuki
中科院分区：
文献类型：
--
作者：
Namekata, Kazuhiko;Harada, Chikako;Harada, Takayuki
青光眼是不可逆性失明的主要原因之一，其特征是视网膜神经节细胞和视神经的进行性变性。虽然青光眼通常与眼压升高有关，但最近的研究表明，在青光眼患者群体中，正常张力性青光眼（NTG）的患病率相对较高。在哺乳动物视网膜中，谷氨酸/天门氨酸转运蛋白（GLAST）定位于Muller胶质细胞。而兴奋性氨基酸载体1 （EAAC1）在包括rgc在内的神经细胞中表达。由于GLAST或EAAC1缺失导致与NTG相似的视网膜变性，我们研究了白细胞介素-1 （IL-1）对GLAST-和EAAC1缺失小鼠RGC死亡的影响。IL-1通过抑制细胞内Na+积累促进Muller细胞中谷氨酸摄取的增加，这是抵消Na+-谷氨酸共转运所必需的。在野生型（WT）、GLAST-和eaac1缺陷小鼠中观察到的谷氨酸摄取增加的趋势是相似的：然而，GLAST缺陷小鼠的谷氨酸摄取和细胞内Na+浓度的基线明显低于野生型小鼠。与此一致的是，IL-1预处理对谷氨酸诱导的glast缺陷小鼠的RGC变性没有任何有益作用。相比之下，IL-1显著增加了野生型和eaac1缺陷小鼠Muller细胞的谷氨酸摄取和存活的RGCs数量。我们的研究结果表明，使用IL-1增强谷氨酸转运蛋白的功能可能有助于视网膜退行性疾病（包括NTG）的神经保护。(c) 2009爱思唯尔爱尔兰有限公司版权所有
Glaucoma, one of the leading causes of irreversible blindness, is characterized by progressive degeneration of retinal ganglion cells (RGCs) and optic nerves. Although glaucoma is often associated with elevated intraocular pressure, recent studies have shown a relatively high prevalence of normal tension glaucoma (NTG) in glaucoma patient populations In the mammalian retina, glutamate/aspartate transporter (GLAST) is localized to Muller glial cells. whereas excitatory amino acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs. Since the loss of GLAST or EAAC1 leads to retinal degeneration similar to that seen in NTG, we examined the effects of interleukin-1 (IL-1) on RGC death in GLAST- and EAAC1-deficient mice. IL-1 promoted increased glutamate uptake in Muller cells by suppressing intracellular Na+ accumulation, which is necessary to counteract Na+-glutamate cotransport The observed trends for the glutamate uptake increase in the wild-type (WT), GLAST- and EAAC1-deficient mice were similar: however, the baseline glutamate uptake and intracellular Na+ concentration in the GLAST-deficient mice were significantly lower than those in the wild-type mice. Consistently, pretreatment with IL-1 exhibited no beneficial effects on glutamate-induced RGC degeneration in the GLAST-deficient mice. In contrast, IL-1 significantly increased glutamate uptake by Muller cells and the number of surviving RGCs in the wild-type and EAAC1-deficient mice. Our findings suggest that the use of IL-1 for enhancing the function of glutamate transporters may be useful for neuroprotection in retinal degenerative disorders including NTG. (c) 2009 Elsevier Ireland Ltd All rights reserved.