Suetsugu-Maki Rinako, Maki Nobuyasu, Fox Timothy P, Nakamura Kenta, Cowper Solari Richard, Tomlinson Craig R, Qu Hongchang, Lambris John D, Tsonis Panagiotis A
Department of Biology and Center for Tissue Regeneration and Engineering at Dayton, University of Dayton, Dayton, OH 45469-2320, USA.
Mol Vis. 2011 Apr 19;17:949-64.
To evaluate the effects of complement employing a mouse model for secondary cataract.
The role of complement receptor C5a (CD88) was evaluated after cataract surgery in mice. An antagonist specific to C5a receptor was administered intraperitoneally to mice. Epithelial to mesenchymal transition (EMT) was evaluated by alpha-smooth muscle actin (α-SMA) staining and proliferation by bromodeoxyuridine (5-bromo-2'-deoxyuridine, BrdU) incorporation. Gene expression patterns was examined by microarray analysis and quantitative polymerase chain reaction (QPCR).
We found that administration of a C5aR antagonist in C57BL/6J mice decreases EMT, as evidenced by α-SMA expression, and cell proliferation. Gene expression by microarray analysis reveals discreet steps of gene regulation in the two major stages that of EMT and lens fiber differentiation in vivo. A hallmark of the microarray analysis is that the antagonist seems to be a novel stage-specific regulator of crystallin genes. At week two, which is marked by lens fiber differentiation genes encoding 12 crystallins and 3 lens-specific structural proteins were severely down-regulated.
These results suggest a possible therapeutic role of an antagonist to C5aR in preventing secondary cataracts after surgery. Also these results suggest that crystallin gene expression can be regulated by pro-inflammatory events in the eye.
利用继发性白内障小鼠模型评估补体的作用。
在小鼠白内障手术后评估补体受体C5a（CD88）的作用。向小鼠腹腔注射C5a受体特异性拮抗剂。通过α平滑肌肌动蛋白（α-SMA）染色评估上皮-间充质转化（EMT），并通过溴脱氧尿苷（5-溴-2'-脱氧尿苷，BrdU）掺入评估增殖情况。通过微阵列分析和定量聚合酶链反应（QPCR）检测基因表达模式。
我们发现，在C57BL/6J小鼠中给予C5aR拮抗剂可减少EMT，这可通过α-SMA表达和细胞增殖得到证明。微阵列分析的基因表达揭示了体内EMT和晶状体纤维分化这两个主要阶段中基因调控的离散步骤。微阵列分析的一个标志是，该拮抗剂似乎是一种新型的晶状体蛋白基因阶段特异性调节剂。在第二周，以编码12种晶状体蛋白和3种晶状体特异性结构蛋白的晶状体纤维分化基因为标志，这些基因被严重下调。
这些结果表明，C5aR拮抗剂在预防术后继发性白内障方面可能具有治疗作用。此外，这些结果表明晶状体蛋白基因表达可受眼中促炎事件的调控。
