Visual neurotoxicity of zinc oxide nanoparticles on zebrafish larvae: Roles of retinal injury, redox imbalance, and impaired phototransduction.

Zinc oxide nanoparticles (ZnO NPs) are extensively used engineered nanomaterials, but their potential to interfere with visual-system development during early vertebrate life stages remains poorly understood. In this study, zebrafish embryos were exposed to ZnO NPs of four sizes (30, 50, 90, and 200 nm) at concentrations of 0.1, 1, and 10 mg/L. ZnO NPs showed marked aggregation and concentration-dependent Zn2+ release, indicating significant particle transformation. At the same time, exposure to ZnO NPs significantly reduced eye area and the eye diameter/body length ratio, disrupted retinal lamination and lens morphology, and impaired multiple visual behaviors, including predation, escape response, phototaxis, locomotor responses during light-dark transitions, and optokinetic response. Moreover, these behavioral impairments increased with higher exposure concentrations and decreased with larger particle sizes. Furthermore, ZnO NPs elevated reactive oxygen species (ROS) levels, decreased catalase (CAT) and superoxide dismutase (SOD) activities and glutathione (GSH) content, enhanced apoptosis, upregulated bax and caspase-3, and downregulated bcl-2, indicating oxidative stress-associated apoptosis. Additionally, expression of phototransduction pathway-related genes opn1mw2, opn1sw1, opn1sw2, and rho was also suppressed, with rho showing the strongest reduction. The study provides new insights into the visual developmental toxicity of ZnO NPs in early vertebrates and offers foundational data and a scientific basis for protecting aquatic ecosystems and maintaining ecological security.