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 μg/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 (V 2 O 5 ) at a concentration of 50 μg/mL. We found that WO 3 , ZnO, V 2 O 5 and CuO ENMs significantly reduced hTCEpi cell viability in comparison to vehicle control

Metal Oxide Engineered Nanomaterials Modulate Rabbit Corneal Fibroblast to Myofibroblast Transformation

“…We determined that V 2 O 5 nanoflakes were moderately toxic to RCFs, consistent with our previous study of corneal epithelial cells in vitro 13 as well as other studies on mammalian cells with V 2 O 3 nanotubes, V 2 O 5 NPs, and V 2 O 5 nanotubes. 51 – 53 In aggregate, these data suggest that nanosized vanadium oxide materials are noxious to cells regardless of their shape or oxidation state.…”

“… 5 , 21 Thus, it was unsurprising that CuO and ZnO NPs exhibited marked cytotoxicity to corneal fibroblasts consistent with previous studies in other ocular cells types including human corneal limbal epithelial cells and fibroblasts, 14 lens epithelial cells, 41 retinal ganglion cells, 42 and retinal photoreceptors. 43 Although CuO and ZnO NPs decreased cell viability and delayed epithelial and fibroblast migration in the present as well as previous studies, 13 , 14 they did not appear to alter KFM transformation in vitro at the concentrations tested. However, ZnO NPs delayed corneal epithelial migration in vivo and prior studies reported that they induced pulmonary fibrosis and increased myofibroblast expression in vivo, 13 , 44 – 50 suggesting that further in vitro and in vivo studies are warranted.…”

“… 43 Although CuO and ZnO NPs decreased cell viability and delayed epithelial and fibroblast migration in the present as well as previous studies, 13 , 14 they did not appear to alter KFM transformation in vitro at the concentrations tested. However, ZnO NPs delayed corneal epithelial migration in vivo and prior studies reported that they induced pulmonary fibrosis and increased myofibroblast expression in vivo, 13 , 44 – 50 suggesting that further in vitro and in vivo studies are warranted.…”

“… 32 The physicochemical and biological properties of MgO, V 2 O 5 , and WO 3 have been presented by our group previously. 13 All the nanomaterials used in this study had a near-spherical shape except V 2 O 5 , which was in the form of a nanoflake. Primary particle diameters as measured by transmission electron microscopy and specific surface area as measured by Brunauer-Emmett-Teller (BET) method are summarized in Supplement A .…”

Review of the Design of Titanium Alloys with Low Elastic Modulus as Implant Materials

“…[48] Furthermore, V also exhibits hepatotoxic and nephrotoxic properties containing glomerulonephritis and pyelonephritis. [48][49][50][51][52] Besides, V compounds have an adverse influence on cell viability, [34,35,53,54] may lead to partial degeneration of the seminiferous epithelium of the seminiferous tubules in the testes, and can affect male fertility. [55][56][57][58][59][60][61][62][63][64] So, the biocompatibility of alloying elements in Ti alloys as implant materials becomes an important research area.…”