Corneal alkali burns are potentially blinding injuries. Alkali induces oxidative stress in corneas followed by excessive corneal inflammation, neovascularization, and untransparent scar formation. Molecular hydrogen (H2), a potent reactive oxygen species (ROS) scavenger, suppresses oxidative stress and enables corneal healing when applied on the corneal surface. The purpose of this study was to examine whether the H2 pretreatment of healthy corneas evokes a protective effect against corneal alkali-induced oxidative stress. Rabbit eyes were pretreated with a H2 solution or buffer solution, by drops onto the ocular surface, and the corneas were then burned with 0.25 M NaOH. The results obtained with immunohistochemistry and pachymetry showed that in the corneas of H2-pretreated eyes, slight oxidative stress appeared followed by an increased expression of antioxidant enzymes. When these corneas were postburned with alkali, the alkali-induced oxidative stress was suppressed. This was in contrast to postburned buffer-pretreated corneas, where the oxidative stress was strong. These corneas healed with scar formation and neovascularization, whereas corneas of H2-pretreated eyes healed with restoration of transparency in the majority of cases. Corneal neovascularization was strongly suppressed. Our results suggest that the corneal alkali-induced oxidative stress was reduced via the increased antioxidant capacity of corneal cells against reactive oxygen species (ROS). It is further suggested that the ability of H2 to induce the increase in antioxidant cell capacity is important for eye protection against various diseases or external influences associated with ROS production.
- MeSH
- alkálie toxicita MeSH
- antioxidancia metabolismus MeSH
- chemické popálení farmakoterapie metabolismus patologie MeSH
- epitelové buňky účinky léků metabolismus patologie MeSH
- hojení ran účinky léků MeSH
- králíci MeSH
- modely nemocí na zvířatech MeSH
- neovaskularizace rohovky prevence a kontrola MeSH
- oxidační stres účinky léků MeSH
- popálení oka chemicky indukované farmakoterapie metabolismus patologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- rohovka krevní zásobení účinky léků metabolismus patologie MeSH
- vodík farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The aim of this study was to examine whether nanofiber scaffolds seeded with rabbit bone marrow mesenchymal stem cells (MSCs nanofibers) transferred onto the damaged corneal surface and covered with cyclosporine A (CsA)-loaded nanofiber scaffolds (CsA nanofibers) enable healing of the rabbit cornea injured with 1N NaOH. The healing of damaged corneas was examined morphologically, immunohistochemically and biochemically on day 24 after the injury. Compared to untreated injured corneas, where corneal ulceration or large corneal thinning or even perforation were developed, injured corneas treated with drug free nanofibers healed without profound disturbances in a majority of cases, although with fibrosis and scar formation. In injured corneas treated with CsA nanofibers or MSCs nanofibers, the development of scar formation was reduced. Best healing results were obtained with a combination of MSCs and CsA nanofibers (MSCs-CsA nanofibers). Corneas healed with highly restored transparency. Neovascularization highly expressed in untreated injured corneas and reduced in corneas treated with CsA nanofibers or MSCs nanofibers, was suppressed in corneas treated with MSCs-CsA nanofibers. The levels of matrix metalloproteinase 9, inducible nitric oxide synthase, interleukin 6, α-smooth muscle actin, tumor growth factor β and vascular endothelial growth factor were significantly decreased in these corneas as compared to untreated corneas, where the levels of the above mentioned markers were high. In conclusion, MSCs-CsA nanofibers were effective in the treatment of severe alkali-induced corneal injury.
- MeSH
- cyklosporin aplikace a dávkování MeSH
- hojení ran účinky léků MeSH
- hydroxid sodný toxicita MeSH
- imunosupresiva aplikace a dávkování MeSH
- jizva prevence a kontrola MeSH
- kaustika toxicita MeSH
- králíci MeSH
- modely nemocí na zvířatech MeSH
- nanovlákna MeSH
- neovaskularizace rohovky prevence a kontrola MeSH
- nosiče léků MeSH
- poranění rohovky terapie MeSH
- systémy cílené aplikace léků metody MeSH
- tkáňové podpůrné struktury MeSH
- transplantace mezenchymálních kmenových buněk metody MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH