The efficacy and safety of tacrolimus for treating nonspecific keratitis in rats caused by alkali burn

Abstract

Objective To investigate the safety and efficacy of tacrolimus (FK506) and dexamethasone in the treatment of nonspecific keratitis in rats induced by alkali burn. Methods A total of 24 rats were randomly divided into four groups in this experimental study: group A (PBS, n=6), group B (dexamethasone, n=6), group C (tacrolimus, n=6) and a control group (no treatment, n=4). Biomicroscopic features, including the opacity of the corneal stroma, the area of corneal neovascularization and epithelial defect, the probability of hyphema, and the number of ulcer cases, were observed and recorded on days 1, 3, 5, 7, 10, 14 after surgery. On days 7 and 14, HE staining was done to observe corneal tissue with infiltrated inflammatory cells. An immunoreaction to vascular endothelial growth factor (VEGF) was detected. Data from multiple groups or two groups at corresponding times were analyzed using a one-way ANOVA and nonparametric Mann-Whitney U test. Results On days 14, the corneal stroma in group C was clear compared to group B (U=2.00,P<0.05). The areas of neovascularization in groups B and C on days 7, 10, and 14 were obviously smaller than the area in group A (U=5.00, 2.00, P<0.05; U=0.00, 0.00, P<0.05; U=0.00, 0.00, P<0.05). The difference between groups B and C was not statistically significant. On days 10 and 14, the areas in groups A and C with epithelial defects were obviously smaller than the area in group B (U=0.00, 0.00, P<0.05; U=0.00, 0.00, P<0.05). The possibility of hyphema in group C was the smallest and no ulcer cases were detected. The hyphema in group B was as severe as group A and many ulcer cases were detected. HE and immunohistochemical staining on days 7 and 14 revealed that the highest number of inflammatory cells infiltrating the corneal stroma and VEGF positive cells was detected in group A, followed by groups B and C (inflammatory cells, U=2.00, 0.00, P<0.05; U=0.00, 0.00, P<0.05. VEGF positive cells, U=0.00, 0.00, P<0.05; U=0.00, 0.00, P<0.05). There were fewer inflammatory cells in group C than in group B on days 7 and 14 (U=0.00, 0.00, P<0.05) and the difference in VEGF positive cells on day 7 was not statistically significant. On day 14, there were fewer VEGF positive cells in group C than in group B (U=3.00, P<0.05). Conclusion Tacrolimus is effective for nonspecific keratitis induced by alkali burn and superior to dexamethasone for safety. Key words: Dexamethasone; Keratitis; Eye burns; Vascular endothelial growth factors; Rats, Sprague-Dawley; Tacrolimus