Protective effects of citicoline-containing eye drops against UVB-Induced corneal oxidative damage in a rat model

It has been reported that citicoline increases antioxidant activity in some tissues. However, the effect of citicoline on corneal wound-healing has not yet been demonstrated. The aim was to investigate the protective effects of citicoline on ultraviolet B (UVB) radiation-induced corneal oxidative damage in a rat model. Four groups (eight animals each) were investigated: controls; UVB only; UVB/citicoline; and citicoline only. Corneal oxidative damage was induced by exposure to UVB radiation at 560 μW/cm2 for five days in the UVB-exposed groups and 1% citicoline eye drops were applied (3xday) for eight days in the two citicoline groups. Corneal surface damage was evaluated by opacity and fluorescein staining. Corneal injury was assessed biochemically by measuring the concentrations of glutathione (GSH) and malondialdehyde (MDA) and the activity of corneal superoxide dismutase (SOD) and catalase. Matrix metalloproteinase (MMP) -2 and -9 and caspase-3 were evaluated by immunofluorescent staining and microscopic examination and by Western blot analysis. Corneal gene expression analysis was performed for vascular endothelial growth factor (VEGF), interleukin-1 beta (IL-1β) and transforming growth factor-beta (TGF-β). UVB radiation caused significant epithelial damage and evident opacity in the cornea, together with a local decrease in SOD, catalase and GSH activity. Corneal MDA concentrations increased with UVB exposure. The UVB/Citicoline group had significantly less corneal damage, greater SOD, catalase and GSH activity, and decreased MDA concentrations compared to the UVB only group (p < 0.05). Expression of TGF-β, IL-1β and VEGF was significantly lower in the citicoline/UVB group compared to the UVB group (p < 0.05). Interestingly, TGF-β expression was lower in the citicoline only group compared with controls. Immunfluorescent staining and Western blot analysis showed increased MMP-2, -9 and caspase-3 in the UVB only group compared with the UVB/citicoline group. It was shown that citicoline treatment may be effective in suppressing oxidative stress and controlling inflammation in UVB corneal injury.