Abnormal glutamate metabolism in the retina of aquaporin 4 (AQP4) knockout mice upon light damage
Abnormal glutamate metabolism in the retina of aquaporin 4 (AQP4) knockout mice upon light damage
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DOI：
10.1007/s10072-013-1610-7
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发表时间：
2014-06
影响因子：
3.3
通讯作者：
Xiu-Miao Li;Ri-le Wendu;Jin Yao;Yan Ren;Yu-xia Zhao;Guofan Cao;Jiang Qin;B. Yan
中科院分区：
文献类型：
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作者：
Xiu-Miao Li;Ri-le Wendu;Jin Yao;Yan Ren;Yu-xia Zhao;Guofan Cao;Jiang Qin;B. Yan
谷氨酸是视网膜中主要的兴奋性神经递质。谷氨酸神经毒性与几种眼部疾病的发病机制有关。水通道蛋白4（AQP4）是一种水选择性膜转运蛋白，其基因敲除可改变视网膜神经元的兴奋性。然而，AQP4基因敲除对视网膜谷氨酸代谢的影响尚不清楚。在这里，我们报道了AQP4基因敲除小鼠的视网膜在光损伤后显示出比野生型小鼠更高的谷氨酸水平。AQP4基因敲除可导致视网膜细胞凋亡加速，反应性胶质增生增加，并减弱RGCs对光损伤的反应。此外，AQP4基因敲除可影响谷氨酸代谢相关蛋白如GLAST和GS的表达模式。总之，这项研究揭示了AQP4在调节谷氨酸代谢中的新作用。AQP4功能的药理学操作可能代表作为一个有效的治疗靶点在治疗神经性眼部疾病。
Glutamate is a major excitatory neurotransmitter in the retina. Glutamate neurotoxicity has been implicated in the pathogenesis of several ocular diseases. Aquaporin 4 (AQP4) is a water-selective membrane transport protein, and its knockout could alter retinal neuron excitability. However, the effect of AQP4 knockout on glutamate metabolism is still unclear in the retina. Here, we reported that the retinas in AQP4 knockout mice showed higher glutamate levels than that in wild-type mice upon light damage. AQP4 knockout could result in accelerated apoptosis of retinal cells, increased reactive gliosis, and attenuated survival of RGCs in response to light damage. Moreover, AQP4 knockout could affect the expression pattern of glutamate metabolism-related proteins such as GLAST and GS. Taken together, this study revealed a novel role of AQP4 in regulating glutamate metabolism. Pharmacological manipulation of AQP4 function may represent as a potent therapeutic target in the treatment of neurological ocular disorders.