Zinc oxide nanoparticles induce human tenon fibroblast apoptosis through reactive oxygen species and caspase signaling pathway

Glaucoma is the leading cause of irreversible blindness in the world and trabeculectomy remains still the most commonly performed filtration surgery. Failure of trabeculectomy is due to the formation of scarring, which is associated with the increased fibroblast proliferation, activation, and collagen deposition at the site of the drainage channel with subconjunctival fibrosis. Our previous study has revealed that zinc oxide (ZnO) nanoparticles could efficiently decrease the expressions of TGF-beta 1 and inhibit fibroblast-mediated collagen lattice contraction. However, the mechanism underlying ZnO nanoparticle-induced fibroblast apoptosis is still unclear. In the present study, we investigated the effect of ZnO nanoparticles on the reactive oxygen species (ROS) and mitochondrial membrane potential (Delta psi m) in human Tenon fibroblasts (HTFs). Moreover, we also explored the influence of ZnO nanoparticles on the expression of Caspase-3, Caspase-9, apoptotic protease-activating factor-1 (Apaf-1), fibroblast-specific protein-1 (FSP-1), collagen III, and E-cadherin. The results indicated that ZnO nanoparticles markedly inhibit HTFs viability and decrease the Delta psi m in a concentration-dependent pattern. Exposure of HTFs to ZnO nanoparticles could also induce the elevated Caspase-3, Caspase-9, and Apaf-1 expression, decrease the levels of FSP-1, collagen III, and E-cadherin expression, leading to HTFs apoptosis. Our results suggested that elevated ROS and activated Caspase signaling play a fundamental role in ZnO nanoparticle-induced HTFs apoptosis.