ISO-1, a macrophage migration inhibitory factor antagonist, prevents N-methyl-D-aspartate-induced retinal damage
ISO-1, a macrophage migration inhibitory factor antagonist, prevents N-methyl-D-aspartate-induced retinal damage
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DOI：
10.1016/j.ejphar.2013.08.041
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发表时间：
2013-10-15
影响因子：
5
通讯作者：
Ishii, Kunio
中科院分区：
文献类型：
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作者：
Naruoka, Taeko;Nakahara, Tsutomu;Ishii, Kunio
巨噬细胞移动抑制因子(MIF)在多种炎症性和免疫介导性疾病中发挥重要作用。炎症反应导致视网膜神经元变性。然而，MIF在视网膜退行性变过程中的作用尚未阐明。在这项研究中，我们确定了MLF的药理抑制是否对N-甲基-对天冬氨酸(NMDA)诱导的大鼠视网膜损伤具有保护作用。玻璃体内注射NMDA(200nmoL)可导致(1)神经节细胞层细胞丢失，内丛状层厚度减少，(2)凋亡细胞增多，(3)小白蛋白阳性无长突细胞减少，(4)白细胞聚集，(5)小胶质细胞激活。注射MIF拮抗剂(S，R)-3-(4-hydroxyphenyl)-4，5-dihydro-5-isoxazole乙酸甲酯，ISO-1,100nmol)可显著减弱上述反应。这些结果表明，ISO-1对视网膜损伤具有保护作用，MIF可能是谷氨酸诱导的兴奋性毒性相关视网膜疾病的神经保护干预的靶点。(C)2013爱思唯尔B.V.保留所有权利。
Macrophage migration inhibitory factor (MIF) has been shown to play an important role in a variety of inflammatory and immune-mediated diseases. The inflammatory responses contribute to retinal neuronal degeneration. However, the role of MIF in the progression of retinal degeneration has not yet been elucidated. In this study, we determined whether pharmacological inhibition of MlF protects against the retinal damage induced by N-methyl-p-aspartate (NMDA) in rats. Intravitreal injection of NMDA (200 nmol) resulted in (1) cell loss in the ganglion cell layer and reduction in the thickness of the inner plexiform layer, (2) an increase in apoptotic cells, (3) a decrease in parvalbumin-positive amacrine cells, (4) accumulation of leukocytes, and (5) microglia activation. Injection of (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1, 100 nmol), a MIF antagonist, significantly attenuated these NMDA-incluced responses. These findings suggest that ISO-1 exerts protective effects against retinal injuries and that MIF may be a target for neuroprotective intervention in retinal diseases associated with glutamate-induced excitotoxicity. (C) 2013 Elsevier B.V. All rights reserved.