Modulation of Retinal Muller Cells by Complement Receptor C5aR
Modulation of Retinal Muller Cells by Complement Receptor C5aR
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DOI：
10.1167/iovs.13-12428
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发表时间：
2013-12-01
影响因子：
4.4
通讯作者：
Lin, Feng
中科院分区：
文献类型：
--
作者：
Cheng, Lijia;Bu, Hong;Lin, Feng
目的。 Muller 细胞是眼睛中发现的一种主要神经胶质细胞类型，被认为在许多视网膜疾病中发挥着重要作用，包括糖尿病视网膜病变 (DR)。补体是先天免疫的重要组成部分，补体的激活与视网膜疾病有关。然而，补体在调节 Muller 细胞功能中的作用仍不清楚。我们试图在这项研究中解决这些问题。方法。使用原代人 Muller 细胞和自发永生化的人 Muller 细胞系，我们在 mRNA 和蛋白质水平上检查了补体受体 C5aR 的表达。研究了前列腺素 E2 和高血糖对 Muller 细胞上 C5aR 表达的调节，这两者都与 DR 密切相关。还通过检查相关细胞因子的产生及其在使用其配体 C5a 连接受体后对视网膜内皮细胞增殖/通透性的影响，研究了 C5aR 对 Muller 细胞的重要性。结果。 C5aR 在人 Muller 细胞中组成型表达。前列腺素 E2 和高血糖单独或协同上调 Muller 细胞中的 C5aR 表达。通过 Muller 细胞上的 C5aR 发出的信号上调 IL-6 和 VEGF 的产生，从而促进人视网膜内皮细胞的增殖并增加其通透性。结论。这些结果表明补体可以通过C5aR调节Muller细胞，这可能有助于包括DR在内的视网膜疾病的发病机制。
PURPOSE. Muller cells, a major type of glial cell found in the eye, are postulated to play an important role in many retinal diseases, including diabetic retinopathy (DR). Complement is an integral part of innate immunity, and the activation of complement has been associated with retinal diseases. However, the role of complement in the regulation of Muller cell function remains unclear. We were trying to address these issues in this study.METHODS. Using primary human Muller cells and a spontaneously immortalized human Muller cell line, we examined the expression of complement receptor C5aR both at mRNA and protein levels. Regulation of C5aR expression on Muller cells by prostaglandin E2 and by hyperglycemia, both of which are integrally involved in DR, were studied. Significance of C5aR on Muller cells was also investigated by examining relevant cytokine productions and their impacts on retinal endothelial cell proliferation/permeability after ligating the receptor using its ligand, C5a.RESULTS. C5aR is constitutively expressed in human Muller cells. Prostaglandin E2 and hyperglycemia individually and synergistically upregulate C5aR expression in Muller cells. Signaling through C5aR on Muller cells upregulates production of IL-6 and VEGF, which promotes the proliferation of human retinal endothelial cells and increases their permeability.CONCLUSIONS. These results indicate that complement can regulate Muller cells through C5aR, which may contribute to the pathogenesis of retinal diseases, including DR.