Carbon monoxide-releasing molecules protect against blue light exposure and inflammation in retinal pigment epithelial cells

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)alpha-induced intercellular adhesion molecule-1 expression. Moreover, it was further observed that CORMs exert their inhibitory effects through blocking nuclear factor-kappa B/p65 nuclear translocation and I kappa B alpha degradation in TNF alpha-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.