Metal Oxide Engineered Nanomaterials Modulate Rabbit Corneal Fibroblast to Myofibroblast Transformation

PURPOSE: Corneal keratocyte-fibroblast-myofibroblast (KFM) transformation plays a critical role in corneal stromal wound healing. However, the impact of engineered nanomaterials (ENMs), found in an increasing number of commercial products, on this process is poorly studied. This study investigates the effects of metal oxide ENMs on KFM transformation in vitro and in vivo. METHODS: Cell viability of rabbit corneal fibroblasts (RCFs) was tested following treatment with 11 metal oxide ENMs at concentrations of 0.5 to 250 µg/ml for 24 hours. Messenger RNA (mRNA) and protein expression of αSMA, a marker of myofibroblast transformation, were measured using RCFs after exposure to 11 metal oxide ENMs at a concentration that did not affect cell viability, in media containing either 0 or 10 ng/ml of TGF-β1. Additionally, the effect of topical Fe(2)O(3) nanoparticles (NPs) (50 ng/ml) on corneal stromal wound healing following phototherapeutic keratectomy (PTK) was determined. RESULTS: V(2)O(5), Fe(2)O(3), CuO, and ZnO ENMs were found to significantly reduce cell viability as compared to vehicle control and the other seven metal oxide ENMs tested. V(2)O(5) nanoflakes significantly reduced mRNA and protein αSMA concentrations in the presence of TGF-β1. Fe(2)O(3) NPs significantly increased αSMA mRNA expression in the presence of TGF-β1 but did not alter αSMA protein expression. Topically applied Fe(2)O(3) NPs in an in vivo rabbit corneal stromal wound healing model did not delay healing. CONCLUSIONS: Fe(2)O(3) NPs promote corneal myofibroblast induction in vitro but do not impair corneal stromal wound healing in vivo. TRANSLATIONAL RELEVANCE: These experimental results can apply to human nanomedical research.