Our previous research revealed that trehalose, a nonreducing disaccharide of glucose and an important stress responsive factor, proved to have anti-inflammatory, antiapoptotic, and particularly antioxidant properties in UVB-irradiated corneas. Trehalose reduced oxidative stress in corneas induced by UVB irradiation, by means of a decrease in the antioxidant/prooxidant imbalance in the corneal epithelium. In this study, we demonstrate that trehalose of 3% or 6% concentration in eye drops directly decreases oxidative stress in UVB-irradiated corneas, by removing the excessive amount of reactive oxygen species (ROS). Trehalose drops applied on corneas during UVB irradiation once daily for four days resulted in a reduction or even absence of the oxidative stress, DNA damage, and peroxynitrite formation (detected by nitrotyrosine residues), seen in buffer-treated corneas. Furthermore, trehalose treatment applied curatively after repeated irradiation for the subsequent fourteen days led to the renewal of corneal transparency and significant suppression or even absence of neovascularization. This was in contrast to buffer-treated irradiated corneas, where the intracorneal inflammation was developed and the untransparent corneas were vascularized. In conclusion, the treatment of UVB-irradiated corneas with trehalose eye drops removed the excessive amount of ROS in the corneal epithelium, leading to the suppression of oxidative stress and favorable corneal healing. The 6% trehalose showed a higher intensive antioxidant effect.

• MeSH
• hojení ran účinky léků   účinky záření   MeSH
• interleukin-1beta metabolismus   MeSH
• keratiny metabolismus   MeSH
• králíci MeSH
• oxidační stres * účinky léků   účinky záření   MeSH
• poranění rohovky farmakoterapie   MeSH
• poškození DNA MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• reepitalizace účinky léků   účinky záření   MeSH
• rohovka účinky léků   patologie   účinky záření   MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• trehalosa farmakologie   terapeutické užití   MeSH
• tyrosin analogy a deriváty   metabolismus   MeSH
• ultrafialové záření * MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The UVB-irradiated cornea is damaged by oxidative stress. Toxic oxygen products induced by UVB radiation in the cornea are insufficiently removed by antioxidants, whose numbers decrease with increasing UVB irradiation. In addition, the UVB-irradiated cornea suffers from hypoxic conditions because damaged corneal cells cannot utilize oxygen normally, although the supply of oxygen to the cornea is unchanged (normal). This contributes to attenuated re-epithelialization, corneal neovascularization and apoptotic cell death. Our previous publications reported that trehalose applied on the corneal surface during irradiation significantly suppressed UVB-induced corneal oxidative damage. The results of this study provide for the first time important evidence that trehalose applied on the surface of corneas for two weeks following repeated UVB irradiation (312 nm, daily dose 0.5 J/cm2) accelerated corneal healing, restored corneal transparency and suppressed corneal neovascularization. Compared to buffered saline treatment, following which caspase-3, nitrotyrosine, malondialdehyde and urokinase-type plasminogen activator were still strongly expressed in the corneal epithelium two weeks after irradiation and corneal neovascularization was evident, apoptotic cell death was already significantly reduced after one week of trehalose application. The expression of other markers of injury returned to normal levels during two weeks of trehalose treatment. In conclusion, our results show that trehalose accelerated healing of the UVB irradiated cornea, very probably via suppression of hypoxia-response injury. In addition, immunohistochemical results on corneal cryostat sections corresponded with those obtained using corneal impression cytologies, thus confirming that corneal impression cytologies are useful for diagnostic purposes.

• MeSH
• aktivátor plasminogenu urokinasového typu metabolismus   MeSH
• apoptóza účinky léků   MeSH
• biologické markery metabolismus   MeSH
• cytodiagnostika metody   MeSH
• experimentální radiační poranění farmakoterapie   metabolismus   patologie   MeSH
• hojení ran účinky léků   MeSH
• imunohistochemie metody   MeSH
• injekce nitrooční MeSH
• kaspasa 3 metabolismus   MeSH
• králíci MeSH
• malondialdehyd metabolismus   MeSH
• nemoci rohovky farmakoterapie   metabolismus   patologie   MeSH
• oxidační stres MeSH
• patologická angiogeneze farmakoterapie   MeSH
• rohovkový epitel účinky záření   MeSH
• trehalosa aplikace a dávkování   terapeutické užití   MeSH
• tyrosin analogy a deriváty   metabolismus   MeSH
• ultrafialové záření MeSH
• zmrazené řezy metody   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Trehalose, a disaccharide of glucose, is a naturally occurring nontoxic and nonreducing bioactive sugar. Trehalose is synthetized by many organisms when cells are exposed to stressful conditions, including dehydration, heat, oxidation, hypoxia or even anoxia. Although trehalose is not synthesized by mammalian cells, it has recently been demonstrated to have a number of important properties that indicate its utility in humans. Trehalose enables wound healing by protecting cells, especially cell membranes, from oxidative injury and dessication. When the injured cornea is treated with trehalose, corneal inflammation, scar formation and corneal neovascularization are suppressed. In dry eye disease, trehalose decreased cell apoptosis and reduced oxidative, inflammatory and proteolytic activity at the ocular surface. In UVB irradiated cornea, trehalose suppressed photodamage evoked by UVB rays. It decreased the intracorneal inflammation and reduced corneal neovascularization. Trehalose prevented postoperative fibrous scar formation after ocular surgery, such as glaucoma filtration surgery. The non-toxicity of trehalose allows its administration in humans for extended periods and enables its use in various disease states.

• MeSH
• antiflogistika chemie   farmakologie   MeSH
• antioxidancia chemie   farmakologie   MeSH
• apoptóza * MeSH
• hojení ran * MeSH
• klinické zkoušky jako téma MeSH
• králíci MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• oftalmologie MeSH
• oxidační stres * MeSH
• rohovka účinky léků   účinky záření   MeSH
• syndromy suchého oka farmakoterapie   MeSH
• trehalosa chemie   farmakologie   MeSH
• ultrafialové záření MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH