Engineered metal oxide nanomaterials inhibit corneal epithelial wound healing in vitro and in vivo

Soohyun Kim, Brooke L. Gates, Brian C. Leonard, Megan M. Gragg, Kent E. Pinkerton, Laura S. Van Winkle, Christopher J. Murphy, Georgios Pyrgiotakis, Zhenyuan Zhang, Philip Demokritou, Sara M. Thomasy

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Ocular exposure to metal oxide engineered nanomaterials (ENMs) is common as exemplified by zinc(II) oxide (ZnO), a major constituent of sunscreens and cosmetics. The ocular surface that includes the transparent cornea and its protective tear film are common sites of exposure for metal ENMs. Despite the frequency of exposure of the ocular surface, there is a knowledge gap regarding the effects of metal oxide ENMs on the cornea in health and disease. Therefore, we studied the effects of metal oxide ENMs on the cornea in the presence or absence of injury. Cell viability of immortalized human corneal epithelial (hTCEpi) cells was assessed following treatment with 11 metal oxide ENMs with a concentration ranging from 0.5 to 250 μg/ml for 24 h. An epithelial wound healing assay with a monolayer of hTCEpi cells was then performed using 11 metal oxide ENMs at select concentrations based on data from the viability assays. Subsequently, based on the in vitro results, in vivo testing of precorneal tear film (PTF) quantity and stability as well as a corneal epithelial wound healing were tested in the presence or absence ZnO or vanadium(V) oxide (V2O5) at a concentration of 50 μg/ml. We found that WO3, ZnO, V2O5 and CuO ENMs significantly reduced hTCEpi cell viability in comparison to vehicle control or the other metal oxide ENMs tested. Furthermore, ZnO and V2O5 ENMs also significantly decreased hTCEpi cell migration. Although ZnO and V2O5 did not alter PTF parameters of rabbits in vivo, corneal epithelial wound healing was significantly delayed by topical ZnO while V2O5 did not alter wound healing. Finally, hyperspectral images confirmed penetration of ZnO and V2O5 through all corneal layers and into the iris stroma. Considering the marked epithelial toxicity and corneal penetration of ZnO, further investigations on the impact of this ENM on the eye are warranted.

Original languageEnglish (US)
Article number100198
StatePublished - Jan 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Materials Science (miscellaneous)
  • Safety, Risk, Reliability and Quality
  • Safety Research
  • Public Health, Environmental and Occupational Health


  • Corneal epithelium
  • Corneal wound healing
  • Metal oxide engineered nanomaterials
  • Nanometals
  • Nanotoxicity


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