Microglia Polarization with M1/M2 Phenotype Changes in rd1 Mouse Model of Retinal Degeneration
Microglia Polarization with M1/M2 Phenotype Changes in rd1 Mouse Model of Retinal Degeneration
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rd1 小鼠视网膜变性模型中小胶质细胞极化与 M1/M2 表型变化
DOI：
10.3389/fnana.2017.00077
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发表时间：
2017-09
影响因子：
2.9
通讯作者：
He Chang
中科院分区：
文献类型：
--
作者：
Zhou Tian;Huang Zijing;Sun Xiaowei;Zhu Xiaowei;Zhou Lingli;Li Mei;Cheng Bing;Liu Xialin;He Chang
小胶质细胞的激活被认为是神经炎症的标志。然而，在视网膜变性过程中，小胶质细胞的激活谱和表型变化尚不清楚。本研究旨在阐明遗传性视网膜变性经典模型rd1 （Pde6βrd1/rd1）小鼠视网膜神经炎症和变性过程中小胶质细胞分布的时空格局和活化小胶质细胞的极化表型。取rd1小鼠不同出生天数（P7、P14、P21、P28、P56、P180）的视网膜进行进一步分析。我们发现大多数CD11b+或IBA1+小胶质细胞在rd1小鼠中表达Ki-67和CD68，并且这些细胞在P14到P28的快速杆变性阶段向退行性光感受器层迁移。这些小胶质细胞表现为典型的阿米巴样活化形态，体圆，树突稀少，而在P180后期，它们表现为静止的分枝形态，树突拉长。流式细胞术显示，rd1视网膜中CD86+CD206- M1小胶质细胞的百分比明显增加，而CD206+CD86- M2小胶质细胞的百分比未见明显变化。有趣的是，介于M1和M2两个极端之间的中间状态CD86+CD206+小胶质细胞在快速杆变性期显著增加。免疫荧光图像显示，rd1小鼠的小胶质细胞高度表达M1标记物，包括CD16/32、CD86和CD40。此外，rd1小鼠的促炎细胞因子（TNF-α、IL-6和CCL2）表达增加。我们的研究结果首次揭示了小胶质细胞在rd1小鼠视网膜变性过程中的独特行为。在快速杆变性阶段，小胶质细胞被激活并特别极化为促炎性M1表型，这表明M1小胶质细胞参与视网膜神经炎症和变性。大多数小胶质细胞在rd1中采用中间极化“M1 1 / 2”状态，表明小胶质细胞在退行性视网膜中协调了复杂的连续光谱。
Microglia activation is recognized as the hallmark of neuroinflammation. However, the activation profile and phenotype changes of microglia during the process of retinal degeneration are poorly understood. This study aimed to elucidate the time-spatial pattern of microglia distribution and characterize the polarized phenotype of activated microglia during retinal neuroinflammation and degeneration in rd1 (Pde6βrd1/rd1) mice, the classic model of inherited retinal degeneration. Retinae of rd1 mice at different postnatal days (P7, P14, P21, P28, P56, and P180) were prepared for further analysis. We found most CD11b+ or IBA1+ microglia expressed Ki-67 and CD68 in rd1 mice and these cells migrated toward the layer of degenerative photoreceptors at the rapid rods degeneration phase from P14 to P28. These microglia exhibited typical ameboid activated shape with round bodies and scarce dendrites, while at late phase at P180, they displayed resting ramified morphology with elongated dendrites. Flow cytometry revealed that the percentage of CD86+CD206- M1 microglia increased markedly in rd1 retinae, however, no significant change was observed in CD206+CD86- M2 microglia. Interestingly, CD86+CD206+ microglia, an intermediate state between the two extremes of M1 and M2, increased markedly at the rapid rods degeneration phase. The immunofluorescence images revealed that microglia in rd1 mice highly expressed M1 markers including CD16/32, CD86, and CD40. In addition, increased expression of pro-inflammatory cytokines (TNF-α, IL-6, and CCL2) was observed in rd1 mice. Our findings unfolded a panorama for the first time that microglia conducted distinctive behaviors with the progression of retinal degeneration in rd1 mice. Microglia is activated and particularly polarized to a pro-inflammatory M1 phenotype at the rapid rods degenerative phase, suggesting that the involvement of M1 microglia in the retinal neuroinflammation and degeneration. Most microglia adopted an intermediate polarization “M1½” state in rd1, revealing that microglia orchestrated a complicated continuous spectrum in degenerative retina.
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影响因子：
4.6
作者：
Leinonen H;Keksa-Goldsteine V;Ragauskas S;Kohlmann P;Singh Y;Savchenko E;Puranen J;Malm T;Kalesnykas G;Koistinaho J;Tanila H;Kanninen KM
通讯作者：
Kanninen KM
影响因子：
4.4
作者：
Scott H. Greenwald;Raymond Farmer;E. Hennessey;K. Bujakowska;Ru Xiao;L. Vandenberghe;E. Pierce
通讯作者：
Scott H. Greenwald;Raymond Farmer;E. Hennessey;K. Bujakowska;Ru Xiao;L. Vandenberghe;E. Pierce
DOI：
10.1016/j.jalz.2019.06.4616
发表时间：
2019-07
期刊：
Alzheimer's & Dementia
影响因子：
--
作者：
S. Liddelow;Kevin A. Guttenplan;L. Clarke;F. C. Bennett;Christopher J. Bohlen;Lucas Schirmer;Mariko L. Bennett-M
通讯作者：
S. Liddelow;Kevin A. Guttenplan;L. Clarke;F. C. Bennett;Christopher J. Bohlen;Lucas Schirmer;Mariko L. Bennett-M
MicroRNA-7靶向Nod样受体蛋白3炎症小体调节帕金森病发病机制中的神经炎症
影响因子：
15.1
作者：
Zhou Y;Lu M;Du RH;Qiao C;Jiang CY;Zhang KZ;Ding JH;Hu G
通讯作者：
Hu G
N-甲基-N-亚硝基脲的时间形貌诱导小鼠视网膜感光细胞变性。
影响因子：
4.6
作者：
Tao Y;Chen T;Fang W;Peng G;Wang L;Qin L;Liu B;Fei Huang Y
通讯作者：
Fei Huang Y