Lens Epithelial Cells Initiate an Inflammatory Response Following Cataract Surgery.
Lens Epithelial Cells Initiate an Inflammatory Response Following Cataract Surgery.
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DOI：
10.1167/iovs.18-25067
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发表时间：
2018-10-01
影响因子：
4.4
通讯作者：
Duncan MK
中科院分区：
文献类型：
--
作者：
Jiang J;Shihan MH;Wang Y;Duncan MK
晶状体上皮细胞(LEC)转化为肌成纤维细胞是导致包括后囊混浊在内的纤维性白内障手术并发症的原因。虽然转化生长因子β信号很重要，但转化生长因子β通路在白内障手术后被激活的机制还不是很清楚。在手术时和24小时后对从小鼠白内障手术模型中获得的晶状体上皮细胞进行RNA-SEQ。用iPathway Guide进行生物信息学分析。免疫荧光法测定细胞的表达动态。LEC转录组在24小时的PCS中发生了巨大的改变。差异表达的基因包括那些对晶状体生物学重要的基因和纤维化标志物。然而，最戏剧性的变化是调节先天免疫反应的基因的表达，最大的三个改变的基因表现出超过1000倍的上调。免疫组织化学结果显示，CXCL1、S100A9、CSF3、COX-2、CCL2、Lcn2和Hmox1蛋白在PCS后1~6h表达上调，在PCS后24小时达到高峰，而在PCS后3d其表达水平急剧下降。这种已知的炎症介质的大量上调先于18h中性粒细胞的眼内渗透，48h的典型转化生长因子β信号的上调，以及3d的巨噬细胞的渗透。这些数据表明，晶状体上皮细胞在晶状体损伤后立即产生促炎细胞因子，可能导致术后炎症反应，并提示炎症可能是晶状体相关纤维化疾病PCS发病的主要因素。
Lens epithelial cell (LEC) conversion to myofibroblast is responsible for fibrotic cataract surgery complications including posterior capsular opacification. While transforming growth factor beta (TGFβ) signaling is important, the mechanisms by which the TGFβ pathway is activated post cataract surgery (PCS) are not well understood. RNA-seq was performed on LECs obtained from a mouse cataract surgery model at the time of surgery and 24 hours later. Bioinformatic analysis was performed with iPathwayGuide. Expression dynamics were determined by immunofluorescence. The LEC transcriptome is massively altered by 24 hours PCS. The differentially expressed genes included those important for lens biology, and fibrotic markers. However, the most dramatic changes were in the expression of genes regulating the innate immune response, with the top three altered genes exhibiting greater than 1000-fold upregulation. Immunolocalization revealed that CXCL1, S100a9, CSF3, COX-2, CCL2, LCN2, and HMOX1 protein levels upregulate in LECs between 1 hour and 6 hours PCS and peak at 24 hours PCS, while their levels sharply attenuate by 3 days PCS. This massive upregulation of known inflammatory mediators precedes the infiltration of neutrophils into the eye at 18 hours PCS, the upregulation of canonical TGFβ signaling at 48 hours PCS, and the infiltration of macrophages at 3 days PCS. These data demonstrate that LECs produce proinflammatory cytokines immediately following lens injury that could drive postsurgical flare, and suggest that inflammation may be a major player in the onset of lens-associated fibrotic disease PCS.
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