Inhibiting Matrix Metalloproteinase 3 Ameliorates Neuronal Loss in the Ganglion Cell Layer of Rats in Retinal Ischemia/Reperfusion
Inhibiting Matrix Metalloproteinase 3 Ameliorates Neuronal Loss in the Ganglion Cell Layer of Rats in Retinal Ischemia/Reperfusion
复制标题
抑制基质金属蛋白酶 3 可改善视网膜缺血/再灌注大鼠神经节细胞层的神经元损失
DOI：
10.1007/s11064-015-1800-1
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发表时间：
2016-05-01
影响因子：
4.4
通讯作者：
Huang，Jufang
中科院分区：
文献类型：
--
作者：
Hu，Tu;You，Qiuting;Huang，Jufang
研究表明基质金属蛋白酶3（MMP 3）通过促进胶质细胞活化、神经元凋亡和脑血屏障损伤参与中枢神经系统的神经元变性。然而，MMP 3是否也参与了视网膜缺血/再灌注诱导的神经元变性仍不确定。本研究检测了MMP 3在成年大鼠视网膜中的细胞定位，并探讨了其表达与视网膜缺血再灌注时神经节细胞层（GCL）神经元丢失的关系。MMP 3在大鼠视网膜各层细胞中广泛表达，包括神经元特异性核蛋白（NeuN）阳性细胞、小白蛋白阳性细胞、钙结合蛋白阳性细胞、蛋白激酶C-α阳性细胞、胶质细胞酸性蛋白阳性细胞、谷氨酰胺合成酶阳性细胞和CD 11b阳性细胞。此外，所有大鼠均接受高眼压（HIOP）处理1 h（h），并在HIOP后6 h、1 d（d）、3 d和7 d处死。与正常对照组相比，HIOP治疗后MMP 3酶原和活性MMP 3的表达均显著上调，但层流分布模式未发生改变。此外，抑制MMP 3改善了HIOP后GCL中NeuN阳性细胞的丢失。总之，我们的数据表明，MMP 3在多种类型的神经元和神经胶质细胞在正常大鼠视网膜表达。同时，其表达和活性的上调与视网膜缺血/再灌注时GCL中神经元的丢失密切相关。
It has been demonstrated that matrix metalloproteinase 3 (MMP3) is integrally involved in the neuronal degeneration of the central nervous system by promoting glial activation, neuronal apoptosis and damage to the brain–blood barrier. However, whether MMP3 also contributes to the neuronal degeneration induced by retinal ischemia/reperfusion is still uncertain. In the present study, we detected the cellular localization of MMP3 in adult rat retinae and explored the relationship of its expression with neuronal loss in the ganglion cell layer (GCL) in retinal ischemia/reperfusion. We found that MMP3 was widely expressed in many cells throughout the layers of the rat retinae, including Vertebrate neuron-specific nuclear protein (NeuN)-, parvalbumin-, calbindin-, protein kinase C-α-, glial fibrillary acidic protein-, glutamine synthetase- and CD11b-positive cells. Furthermore, all rats were treated with high intraocular pressure (HIOP) for 1 h (h) and sacrificed at 6 h, 1 day (d), 3 d, and 7 d after HIOP. Compared to the normal control, the expression of both proenzyme MMP3 and active MMP3 were significantly up-regulated after HIOP treatment without alteration of the laminar distribution pattern. Moreover, inhibiting MMP3 ameliorated the loss of NeuN-positive cells in the GCL following HIOP. In summary, our data demonstrates that MMP3 is expressed in multiple types of neurons and glial cells in normal rat retinae. Simultaneously, the up-regulation of its expression and activity are closely involved in neuronal loss in the GCL in retinal ischemia/reperfusion.