Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Biomed Pharmacother. 2018 Jul;103:517-523. doi: 10.1016/j.biopha.2018.04.038. Epub 2018 Apr 24.
Age-related macular degeneration (AMD) is a multifactorial disease resulting in the gradual loss of retinal pigment epithelium (RPE) and the permanent visual damage. Various risk factors, including oxidative stress, form a complex network at the confluence of inflammation. Mesenchymal stem cell (MSC) is a well-studied population of adult stem cell with strong neuroprotective and immunoregulatory properties. Here, we reported the protective effect of MSC on sodium iodate (NaIO3)-triggered RPE degeneration. Sodium iodate (NaIO3)-induced RPE cell death was remarkably reduced when cocultured with MSC. Inhibition of several cell death pathways mediated by mitochondrial instability and its subsequent caspase-1/3/8 activation was implicated in this process. In addition, NLRP3 inflammasome, the upstream of caspase-1 activation, was also found downregulated via suppressing its priming signal NF-κB pathway. Taken together, MSC protected against NaIO3-triggered RPE death via deactivating NF-κB-mediated NLRP3 inflammasome and maintaining mitochondrial integrity. This study highlights the significant role of MSC in modulating the proinflammatory environment of AMD, and suggests the clinical value of MSC in treating AMD as well as RPE replacement therapy.
年龄相关性黄斑变性（AMD）是一种多因素疾病，导致视网膜色素上皮（RPE）逐渐丧失和永久性视觉损伤。各种风险因素，包括氧化应激，在炎症的汇合处形成一个复杂的网络。间充质干细胞（MSC）是一种研究得很好的成人干细胞，具有很强的神经保护和免疫调节特性。在这里，我们报告了 MSC 对碘酸钠（NaIO3）引发的 RPE 变性的保护作用。当与 MSC 共培养时，NaIO3 诱导的 RPE 细胞死亡明显减少。线粒体不稳定及其随后的半胱天冬酶-1/3/8 激活介导的几种细胞死亡途径的抑制参与了这一过程。此外，还发现通过抑制其初始信号 NF-κB 途径，NLRP3 炎性小体，半胱天冬酶-1 激活的上游，也被下调。总之，MSC 通过失活 NF-κB 介导的 NLRP3 炎性小体和维持线粒体完整性来保护 RPE 免受 NaIO3 触发的死亡。这项研究强调了 MSC 在调节 AMD 促炎环境中的重要作用，并表明 MSC 在治疗 AMD 以及 RPE 替代治疗方面具有临床价值。
