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

ABSTRACT: Ocular exposure to metal oxide engineered nanomaterials (ENMs) is common as exemplified by zinc 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 ?g/mL for 24 hours. 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 pentoxide (V₂O₅) at a concentration of 50 ?g/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.

SUBMITTER: Kim S

PROVIDER: S-EPMC7062360 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Engineered metal oxide nanomaterials inhibit corneal epithelial wound healing <i>in vitro</i> and <i>in vivo</i>.

Kim Soohyun S Gates Brooke B Leonard Brian C BC Gragg Megan M Pinkerton Kent E KE Winkle Laura Van LV Murphy Christopher J CJ Pyrgiotakis Georgios G Zhang Zhenyuan Z Demokritou Philip P Thomasy Sara M SM

NanoImpact 20191206

Ocular exposure to metal oxide engineered nanomaterials (ENMs) is common as exemplified by zinc 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 EN ...[more]

PMID: 32154443

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Project description:Following injury, corneal stromal keratocytes transform into repair-phenotype of activated stromal fibroblasts (SFs) and participate in wound repair. Simultaneously, ongoing bi-directional communications between corneal stromal-epithelial cells also play a vital role in mediating the process of wound healing. Factors produced by stromal cells are known to induce proliferation, differentiation, and motility of corneal epithelial cells, which are also subsequently the main processes that occur during wound healing. In this context, the present study aims to investigate the effect of SFs conditioned medium (SFCM) on corneal epithelial cell function along with substance P (SP). Antibody microarrays were employed to profile differentially expressed cell surface markers and cytokines in the presence of SFCM and SP. Antibody microarray data revealed enhanced expression of the ITGB1 in corneal epithelial cells following stimulation with SP whereas SFCM induced abundant expression of IL-8, ITGB1, PD1L1, PECA1, IL-15, BDNF, ICAM1, CD8A, CD44 and NTF4. All these proteins have either direct or indirect roles in epithelial cell growth, movement and adhesion related signaling cascades during tissue regeneration. We also observed activation of MAPK signaling pathway along with increased expression of focal adhesion kinase (FAK), paxillin, vimentin, ?-catenin and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Additionally, epithelial-to-mesenchymal transition (EMT) regulating transcription factors Slug and ZEB1 expression were enhanced in the presence of SFCM. SP enriched the expression of integrin subunits ?4, ?5, ?V, ?1 and ?3 whereas SFCM increased ?4, ?5, ?V, ?1 and ?5 integrin subunits. We also observed increased expression of Serpin E1 following SP and SFCM treatment. Wound healing scratch assay revealed enhanced migration of epithelial cells following the addition of SFCM. Taken together, we conclude that SFCM-mediated sustained activation of ZEB1, Slug in combination with upregulated migration-associated integrins and ERK (Extracellular signal-regulated kinase)-FAK-paxillin axis, may lead to induce type 2 EMT-like changes during corneal epithelial wound healing.

Dataset Information

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

Publications

Engineered metal oxide nanomaterials inhibit corneal epithelial wound healing <i>in vitro</i> and <i>in vivo</i>.

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