Department of Ophthalmology, Chiayi Christian Hospital, Chiayi 60002, Taiwan, R.O.C.
Department of Ophthalmology, Kaohsiung Municipal Hsiao‑kang Hospital, Kaohsiung 81267, Taiwan, R.O.C.
Int J Mol Med. 2020 Sep;46(3):1096-1106. doi: 10.3892/ijmm.2020.4656. Epub 2020 Jun 23.
The most common cause of vision loss among the elderly is age‑related macular degeneration (AMD). The aim of the present study was to investigate the potential cytoprotective and anti‑inflammatory effects of carbon monoxide‑releasing molecules (CORMs), and their ability to activate the expression of nuclear factor erythroid 2‑related factor 2 (Nrf2)‑related genes in human retinal pigment epithelium (RPE) cells, as well as the inhibition of endothelial cell migration. It was first determined that CORM2 and CORM3 suppressed blue light‑induced cell damage. In addition, a decrease in the level of cleaved poly(ADP‑ribose) polymerase 1 protein and dissipation of mitochondrial membrane potential were considered to reflect the anti‑apoptotic activity of CORMs. Furthermore, CORM2 induced Nrf‑2 activation and the expression of the Nrf2‑related genes heme oxygenase‑1 and glutamate‑cysteine ligase. Pretreatment with CORM2 abolished the blue light‑induced increase in oxidative stress, suggesting that CORM2‑induced antioxidant activity was involved in the cytoprotection against blue light. It was also demonstrated that CORMs markedly suppressed tumor necrosis factor (TNF)α‑induced intercellular adhesion molecule‑1 expression. Moreover, it was further observed that CORMs exert their inhibitory effects through blocking nuclear factor‑κB/p65 nuclear translocation and IκBα degradation in TNFα‑treated RPE cells. It was observed that CORM2, but not CORM3, protected against oxidative stress‑induced cell damage. CORMs abolished vascular endothelial growth factor‑induced migration of endothelial cells. The findings of the present study demonstrated the cytoprotective, antioxidant and anti‑inflammatory effects of CORMs on RPE cells and anti‑angiogenic effects on endothelial cells, suggesting the potential clinical application of CORMs as anti‑AMD agents.
老年人视力丧失的最常见原因是年龄相关性黄斑变性（AMD）。本研究旨在探讨一氧化碳释放分子（CORM）的潜在细胞保护和抗炎作用，以及它们激活人视网膜色素上皮（RPE）细胞中核因子红细胞 2 相关因子 2（Nrf2）相关基因表达的能力，以及抑制内皮细胞迁移的能力。首先确定 CORM2 和 CORM3 抑制蓝光诱导的细胞损伤。此外，减少聚（ADP-核糖）聚合酶 1 蛋白的裂解水平和线粒体膜电位的耗散被认为反映了 CORM 的抗凋亡活性。此外，CORM2 诱导 Nrf-2 激活和 Nrf2 相关基因血红素加氧酶-1 和谷氨酸-半胱氨酸连接酶的表达。用 CORM2 预处理可消除蓝光诱导的氧化应激增加，表明 CORM2 诱导的抗氧化活性参与了对蓝光的细胞保护作用。还表明 CORMs 显著抑制肿瘤坏死因子（TNF）α诱导的细胞间黏附分子-1 表达。此外，还进一步观察到 CORMs 通过阻断 TNFα 处理的 RPE 细胞中核因子-κB/p65 核易位和 IκBα 降解来发挥其抑制作用。观察到 CORM2 而不是 CORM3 可防止氧化应激诱导的细胞损伤。CORMs 消除了血管内皮生长因子诱导的内皮细胞迁移。本研究的结果表明 CORMs 对 RPE 细胞具有细胞保护、抗氧化和抗炎作用，以及对内皮细胞的抗血管生成作用，表明 CORMs 作为抗 AMD 药物具有潜在的临床应用前景。
