원문정보
초록
영어
To treat vision-threatening complications of diabetic retinopathy, it is important to develop effective and safe therapeutics to suppress retinal neovascularization. In this study, we investigated whether titanium dioxide (TiO2) nanoparticles maintain antiangiogenic effect on retinal neovascularization even at the concentration without definite toxicity. TiO2 nanoparticles do not induce cellular toxicity on 3 different cell lines representing vascular, neuronal, and perineural glial cells even at 100 times the presumptive therapeutic concentration (105 nanoparticles per cell, 130.47 ng/ml). Furthermore, they do not result in histologic abnormalities and significant change in gene expression at the presumptive toxic concentration (10 times the presumptive therapeutic concentration, 106 nanoparticles per cell, 1.30 μg/ml). Interestingly, TiO2 nanoparticles inhibit tube formation and migration of endothelial cells at the presumptive therapeutic concentration. In addition, they suppress ischemia-induced retinal neovascularization in mice model of oxygen-induced retinopathy at the same concentration. In particular, the antiangiogenic effect of TiO2 nanoparticles comes from the suppression of angiogenic processes mediated by suppression of vascular endothelial growth factor receptor-2/mitogen- activated protein kinase pathway. Taken together, our results demonstrate that TiO2 nanoparticles can exert antiangiogenic effect on retinal neovascularization at the concentration without genetic, cellular, and histologic toxicity, suggesting possible application in the treatment of diabetic retinopathy.