Abstract
Although the wound healing effects of nitric oxide (NO) are known, the mechanism by which NO modulates corneal wound healing remains unclear. In this study, we investigated the effect of exogenous NO donor (NaNO2) on corneal wound healing. We found that NaNO2 (0.1 μM to 100 μM) increased human corneal epithelial cell (HCEC) viability and migration. It also modulated the phosphorylation of mitogen-activated protein kinases (MAPKs) in a time- dependent manner in those HCECs. Further, p38 MAPK phosphorylation increased at 6 h and normalized at 24 h, while the phosphorylation of extracellular signal regulated kinase (ERK) was increased both at 6 h and 24 h. Topical treatment with NaNO2 (10 μM) enhanced corneal epithelial healing and decreased corneal opacity in murine corneal alkali burn model by modulating inflammatory cytokines. Our findings suggest that NO increased HCEC proliferation and migration via time-dependent MAPK activation and eventually enhanced corneal recovery from the alkali burn.
Highlights
Nitric oxide (NO) is a small signaling molecule with various biological functions
It is noteworthy that a high concentration of nitric oxide (NO) (100 mM of NaNO2) resulted in a cytotoxic effect, even at 6 h incubation, and this toxic effect only increased with the length of incubation (Fig. 1)
Our study found that mitogen-activated protein kinases (MAPKs) phosphorylation was modulated by NaNO2; both time- and dose-dependently, NaNO2 (0.1 to 1000 μM) significantly increased extracellular signal regulated kinase (ERK) phosphorylation of human corneal epithelial cells (HCEC) when measured at 6 h after exposure
Summary
Nitric oxide (NO) is a small signaling molecule (free radical) with various biological functions. In a skin wound model, NO is produced by various cells involved in wound healing. Tissue injury results in the excessive accumulation of reactive oxygen species (ROS), such as superoxide and hydroxyl radical (O2− and OH·), at the injury site[9]. These ROS play an important role in initiating the wound healing response, regulating inflammation and defending the host from invasive microorganisms. It has been shown to promote corneal epithelial wound healing in cell and animal models. In this study we investigated the effect of exogenous NO on primary culture of human corneal epithelial cells (HCEC) and in a murine corneal alkali burn model. A murine corneal alkali burn model was treated with topical NO application and the rate of corneal healing via inflammatory cytokine modulation was investigated
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