Kim, K.T., Zaikova, T., Hutchison, J.E., and Tanguay, R.L. (2013) Gold Nanoparticles Disrupt Zebrafish Eye Development and Pigmentation. Toxicological sciences : an official journal of the Society of Toxicology. 133(2):275-88.
Systematic toxicological study is still required to fully understand the hazard potentials of gold nanoparticles (AuNPs).
Because their biomedical applications are rapidly evolving, we investigated developmental toxicity of AuNPs in an in vivo embryonic zebrafish model at exposure concentration ranges from 0.08 to 50 mg/l. Exposure of zebrafish embryos to 1.3 nm
AuNPs functionalized with a cationic ligand, N,N,N trimethylammoniumethanethiol (TMAT-AuNPs), resulted in smaller malpigmented eyes. We determined that TMAT-AuNPs caused a
significant increase of cell death in the eye, which was correlated with an increase in gene expression of p53 and bax. Expression patterns of key transcription factors regulating eye development (pax6a, pax6b, otx2 and rx1) and pigmentation (sox10) were both repressed in a concentration-dependent manner in embryos exposed to TMAT-AuNPs. Reduced spatial localization of
pax6a, rx1, sox10 and mitfa was observed in embryos by whole-mount in-situ hybridization. The swimming behavior of embryos exposed to sublethal concentrations of TMAT-AuNPs showed hypo-activity and
embryos exhibited axonal growth inhibition. Overall, these results demonstrated that TMAT-AuNPs disrupt the progression of
eye development and pigmentation that continues to behavioral and neuronal damage in the developing zebrafish.