Regional Expression of Act-MMP3 Contributes to the Selective Loss of Neurons in Ganglion Cell Layers following Acute Retinal ischemia/Reperfusion Injury
Regional Expression of Act-MMP3 Contributes to the Selective Loss of Neurons in Ganglion Cell Layers following Acute Retinal ischemia/Reperfusion Injury
复制标题
Act-MMP3 的区域表达导致急性视网膜缺血/再灌注损伤后神经节细胞层神经元的选择性丢失
DOI：
10.1080/02713683.2019.1684523
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发表时间：
2019-11-08
影响因子：
2
通讯作者：
Huang, Jufang
中科院分区：
文献类型：
--
作者：
Hu, Tu;Wang, Shuchao;Huang, Jufang
目的：有证据表明，在缺血/再灌注事件期间，神经节细胞层（GCL）中的神经元损失首先发生在外周视网膜，然后是中央视网膜。然而，这一关键分子或因素介导的选择性损失需要阐明。本研究检测了急性视网膜缺血/再灌注（RI/R）损伤后大鼠中央和外周视网膜中活性基质金属蛋白酶3（Act-MMP 3）的局部表达，探讨其在GCL选择性神经元丢失中的作用及其机制。方法：采用QPCR和Western Blotting方法检测Act-MMP 3在成年大鼠视网膜中央部和周边部的表达。免疫荧光和双重免疫荧光用于评估GCL中NeuN阳性细胞的数量，并测定Iba-1+CD 68阳性细胞。此外，进行线性回归分析以检验Act-MMP 3的ODV与视网膜中GCL/Iba-1+CD 68阳性细胞中神经元损失之间的相关性。结果如下：急性RI/R后，周边区活性基质金属蛋白酶3（Act-MMP 3）表达明显高于中央区。我们发现Act-MMP 3的上调与GCL中的选择性神经元丢失相关（中央：r = 0.7566，p <0.0001，r（2）= 0.5724;外周：r = 0.8241，p <0.0001，r（2）= 0.6792）。抑制Act-MMP 3可改善急性RI/R后GCL的选择性神经元丢失。此外，周边视网膜中的小胶质细胞的活化也先于中央视网膜中的小胶质细胞的活化，并且被发现与Act-MMP 3的区域表达相关（中央：r = 0.8540，p < .0001，r（2）= 0.7294;周边：r = 0.7820，p < .0001，r（2）= 0.6116）。抑制Act-MMP 3可减轻急性RI/R后小胶质细胞的局部活化。结论：Act-MMP 3在大鼠视网膜的局部表达可能与急性RI/R时GCL的选择性神经元丢失和小胶质细胞的局部激活有关。
Purpose: Evidences suggest that during ischemia/reperfusion events, neuronal loss in ganglion cell layers (GCLs) occurs initially in the peripheral retinae followed by the central. However, which key molecule or factor mediates this selective loss needs elucidation. In the present study, we detected the regional expression of active matrix metalloproteinase 3 (Act-MMP3) in the central and peripheral rat retinae following acute retinal ischemia/reperfusion (RI/R) injury and explored the effects and mechanisms of this regional expression on the selective neuronal loss in GCLs. Methods: QPCR and Western Blotting were used to detect the expression of Act-MMP3 in the central part and peripheral part of the adult rat retinae. Immunofluorescence and double immunofluorescence were used to assess the number of NeuN-positive cells in the GCLs and Iba-1+CD 68-positive cells were determined. Additionally, the Linear-regression analysis was performed to test the correlation between the ODV of Act-MMP3 and the neuronal loss in the GCLs/Iba-1+CD 68 positive cells in retinae. Results: An evident up-regulation of active matrix metalloproteinase 3 (Act-MMP3) in peripheral retinae preceded to that in central region following acute RI/R. We found Act-MMP3 up-regulation to be associated with the selective neuronal loss in GCLs (central: r = 0.7566, p < .0001, r(2) = 0.5724; peripheral: r = 0.8241, p < .0001, r(2) = 0.6792). Suppressing Act-MMP3 ameliorated the selective neuronal loss in GCLs following acute RI/R. Furthermore, the activation of microglia in the peripheral retinae also preceded to that in the central and was found to be correlated with the regional expression of Act-MMP3 (Central: r = 0.8540, p < .0001, r(2) = 0.7294; Peripheral: r = 0.7820, p < .0001, r(2) = 0.6116). Suppressing Act-MMP3 ameliorated the microglia regional activation following acute RI/R. Conclusion: The regional expression of Act-MMP3 in the rat retinae may contribute to the selective neuronal loss in GCLs and microglia regional activation in acute RI/R.