Retinal Injury Activates Complement Expression in Müller Cells Leading to Neuroinflammation and Photoreceptor Cell Death.
Retinal Injury Activates Complement Expression in Müller Cells Leading to Neuroinflammation and Photoreceptor Cell Death.
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视网膜损伤激活了导致神经炎症和感光细胞死亡的Müller细胞中的补体表达。
DOI：
10.3390/cells12131754
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发表时间：
2023-06-30
期刊：
影响因子：
6
通讯作者：
Connor, Kip M. M.
中科院分区：
文献类型：
--
作者：
Tabor, Steven J. J.;Yuda, Kentaro;Deck, Jonathan;Gnanaguru, Gopalan;Connor, Kip M. M.
视网膜脱离(RD)是由过多的临床症状引起的一种神经退行性致盲疾病。RD的特征是视网膜与视网膜色素上皮(RPE)的物理分离，最终导致光感受器细胞死亡、炎症和视力丧失。尽管补体的激活在RD的发病机制中起着关键作用，但补体产生的视网膜细胞来源仍然难以捉摸。在这里，使用C3tdTomato报告小鼠，我们表明视网膜损伤上调了C3的表达，特别是在Müler细胞。补体激活级联导致产生促炎症裂解产物C3a和C5a，分别与C3aR和C5aR1结合。我们的流式细胞仪数据显示，视网膜损伤显著上调了小胶质细胞中的C3aR和C5aR1，并导致了外周免疫细胞的渗透。C3、C5、C3aR或C5aR1的缺失减少了光感受器细胞的死亡，减少了小胶质细胞和外周免疫细胞向视网膜下腔的渗透。这些结果表明，C3/C3aR和C5/C5aR1在诱导视网膜色素变性和炎症反应中起重要作用。
Retinal detachment (RD) is a neurodegenerative blinding disease caused by plethora of clinical conditions. RD is characterized by the physical separation of retina from the underlying retinal pigment epithelium (RPE), eventually leading to photoreceptor cell death, inflammation, and vision loss. Albeit the activation of complement plays a critical role in the pathogenesis of RD, the retinal cellular source for complement production remains elusive. Here, using C3 tdTomato reporter mice we show that retinal injury upregulates C3 expression, specifically in Müller cells. Activation of the complement cascade results in the generation of proinflammatory cleaved products, C3a and C5a, that bind C3aR and C5aR1, respectively. Our flow cytometry data show that retinal injury significantly upregulated C3aR and C5aR1 in microglia and resulted in the infiltration of peripheral immune cells. Loss of C3, C5, C3aR or C5aR1 reduced photoreceptor cell death and infiltration of microglia and peripheral immune cells into the sub-retinal space. These results indicate that C3/C3aR and C5/C5aR1 play a crucial role in eliciting photoreceptor degeneration and inflammatory responses in RD.
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DOI：
10.1523/jneurosci.0897-18.2018
发表时间：
2018-10-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Matsumoto H;Sugio S;Seghers F;Krizaj D;Akiyama H;Ishizaki Y;Gailly P;Shibasaki K
通讯作者：
Shibasaki K
影响因子：
9.3
作者：
Schartz ND;Tenner AJ
通讯作者：
Tenner AJ
影响因子：
64.8
作者：
Carvelli, Julien;Demaria, Olivier;Vivier, Eric
通讯作者：
Vivier, Eric
DOI：
10.1161/atvbaha.107.160580
发表时间：
2008-03-01
影响因子：
8.7
作者：
Kastl, Stefan P.;Speidl, Walter S.;Wojta, Johann
通讯作者：
Wojta, Johann
DOI：
10.3791/50660
发表时间：
2013-09-11
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Matsumoto H;Miller JW;Vavvas DG
通讯作者：
Vavvas DG