Cataract Surgery Induces Retinal Pro-inflammatory Gene Expression and Protein Secretion
Cataract Surgery Induces Retinal Pro-inflammatory Gene Expression and Protein Secretion
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DOI：
10.1167/iovs.10-6001
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发表时间：
2011-01-01
影响因子：
4.4
通讯作者：
Lois, Noemi
中科院分区：
文献类型：
--
作者：
Xu, Heping;Chen, Mei;Lois, Noemi
目的.采用实验性啮齿动物模型研究白内障手术对视网膜中促炎基因和蛋白表达的影响。在C57 BL/6小鼠（n = 24）的一只眼睛中进行囊外透镜摘除;对侧未手术的眼睛（n = 24）以及未手术动物的眼睛（n = 9）作为对照。术后收集神经感觉视网膜和视网膜色素上皮（RPE）/脉络膜。通过实时PCR和选择性荧光化学法检测参与急性炎症/损伤反应的基因表达，包括IL-1 β、成纤维细胞生长因子、转化生长因子β、趋化因子CCL 2、SDF-1和补体C3、C4和因子B（CF B）。IL-1 β和CCL 2基因的表达在术后30分钟在感觉神经视网膜中显著上调（> 20倍，P < 0.01），并维持2周的术后观察期; IL-1 β在RPE/脉络膜中的表达也上调。在感觉神经视网膜中补体C3（> 5倍）和CFB（> 30倍）基因的表达也显著上调（两种情况下均P < 0.01）。共聚焦显微镜下观察到IL-1b、CCL 2和CFB以及C5 b-9免疫染色增强。在啮齿类动物中，透镜摘除在眼后段引起急性促炎基因和蛋白质反应，表明炎性小体的诱导以及补体激活，如在“危险”反应中发生的那样。人类类似的反应可能解释了白内障手术相关视网膜并发症如黄斑囊样水肿的发病机制。（Invest Ophthalmol维斯科学。2011; 52：249-255）DOI：10.1167/iovs.10-6001
PURPOSE. To investigate the effect(s) of cataract surgery on the expression of pro-inflammatory genes and proteins in the retina using an experimental rodent model.METHODS. An extracapsular lens extraction was performed in one eye of C57BL/6 mice (n = 24); the contralateral unoperated eyes (n = 24) as well as eyes from unoperated animals (n = 9) served as controls. The neurosensory retina and retinal pigment epithelium (RPE)/choroid were collected postoperatively. Expression of genes involved in the acute inflammatory/injury response, including IL-1 beta, fibroblast growth factor, transforming growth factor beta, chemokine CCL2, SDF-1, and complements C3, C4, and factor B (CFB), were examined by real-time PCR and, selectively, by immunohistochemistry.RESULTS. The expression of IL-1 beta and CCL2 genes was markedly upregulated (> 20-fold, P < 0.01) in the neurosensory retina 30 minutes postoperatively and maintained for the 2-week postoperative period of observation; IL-1 beta expression was also upregulated in RPE/choroid. The expression of complement C3 (> 5-fold) and CFB (> 30-fold) genes in the neurosensory retina was also significantly upregulated (P < 0.01 in both cases). Increased IL-1b, CCL2, and CFB as well as enhanced C5b-9 immunostaining were observed by confocal microscopy.CONCLUSIONS. In rodents, lens extraction elicited an acute pro-inflammatory gene and protein response in the posterior segment of the eye, indicating induction of the inflammasome as well as complement activation, as occurs in the "danger" response. A similar response in humans might explain the pathogenesis of cataract surgery-associated retinal complications such as cystoid macular edema. (Invest Ophthalmol Vis Sci. 2011; 52: 249-255) DOI: 10.1167/iovs.10-6001