Carbon monoxide­releasing molecules protect against blue light exposure and inflammation in retinal pigment epithelial cells.

The most common cause of vision loss among the elderly is age­related macular degeneration (AMD). The aim of the present study was to investigate the potential cytoprotective and anti­inflammatory effects of carbon monoxide­releasing molecules (CORMs), and their ability to activate the expression of nuclear factor erythroid 2­related 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 light­induced cell damage. In addition, a decrease in the level of cleaved poly(ADP­ribose) polymerase 1 protein and dissipation of mitochondrial membrane potential were considered to reflect the anti­apoptotic activity of CORMs. Furthermore, CORM2 induced Nrf­2 activation and the expression of the Nrf2­related genes heme oxygenase­1 and glutamate­cysteine ligase. Pretreatment with CORM2 abolished the blue light­induced increase in oxidative stress, suggesting that CORM2­induced antioxidant activity was involved in the cytoprotection against blue light. It was also demonstrated that CORMs markedly suppressed tumor necrosis factor (TNF)α­induced intercellular adhesion molecule­1 expression. Moreover, it was further observed that CORMs exert their inhibitory effects through blocking nuclear factor­κB/p65 nuclear translocation and IκBα degradation in TNFα­treated RPE cells. It was observed that CORM2, but not CORM3, protected against oxidative stress­induced cell damage. CORMs abolished vascular endothelial growth factor­induced migration of endothelial cells. The findings of the present study demonstrated the cytoprotective, antioxidant and anti­inflammatory effects of CORMs on RPE cells and anti­angiogenic effects on endothelial cells, suggesting the potential clinical application of CORMs as anti­AMD agents.