Department of Ophthalmology, Dongguk University, Ilsan Hospital, Goyang, South Korea.
Department of Ophthalmology and Visual Sciences, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Sci Rep. 2017 Aug 14;7(1):8093. doi: 10.1038/s41598-017-08576-9.
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 (NaNO) on corneal wound healing. We found that NaNO (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 NaNO (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.
虽然一氧化氮（NO）的伤口愈合作用是已知的，但 NO 调节角膜伤口愈合的机制仍不清楚。在这项研究中，我们研究了外源性 NO 供体（NaNO）对角膜伤口愈合的影响。我们发现 NaNO（0.1 μM 至 100 μM）可增加人角膜上皮细胞（HCEC）的活力和迁移。它还以时间依赖性方式调节那些 HCEC 中丝裂原活化蛋白激酶（MAPKs）的磷酸化。此外，p38 MAPK 磷酸化在 6 小时时增加，并在 24 小时时恢复正常，而细胞外信号调节激酶（ERK）的磷酸化在 6 小时和 24 小时时均增加。通过调节炎性细胞因子，局部应用 NaNO（10 μM）增强了小鼠角膜碱烧伤模型中的角膜上皮愈合并降低了角膜混浊度。我们的研究结果表明，NO 通过时间依赖性 MAPK 激活增加 HCEC 的增殖和迁移，最终增强了角膜从碱烧伤中的恢复。
