RESUMO
Objective To investigate the histopathological and ultrastructural changes of corneal epithelium induced by erlotinib in mice.Methods Totally 30 6-8 weeks old male BALB/c mice were divided into three groups:Control group (n =12),experimental group (n =12),another 6 mice did nothing as the blank control.Experimental group used erlotinib eye drops and control group used PBS in both eyes,four times per day.At 1 day,7 days and 14 days after the intervention,corneal fluorescence staining (FL) was observed by slit lamp and graded.On the fourteenth day after the intervention,the eye balls of mice were taken,and the histopathological and ultrastructural changes of corneal epithelium and epithelial cells were observed by optical microscope and electron microscope,respectively.And protein of cornea was measured by Western Blot.Results Before the intervention,there was no significant difference in FL scores between the experimental group and control group (P ＞ 0.05).At 1 day,7 days and 14 days,FL score of experimental group was significantly higher than the groups of non-intervention,the difference was statistically significant (all P ＜ 0.05).While FL score of control group was not statistically significant before and after intervention (all P ＞ 0.05);Compared between two groups,there were statistical differences at 7 days,14 days in FL score (all P ＜ 0.05).In the experimental group,the histopathological changes of murine corneal epithelial cells had disorderly arrangement,increased layers of cells,and the inflammatory cells.Under electron microscope,the morphology of corneal epithelial surface cells was irregular and partially detached.The number of microvilli,desmosomes and hemidesmosomes were significantly decreased when compared to the control group.The expression of p-EGFR in experimental group was significantly less than that in control group,the difference was statistically significant (P ＜ 0.05).Conclusion Erlotinib can damage the tissue structure of corneal epithelium and ultrastructure of corneal epithelial cells in mice.And the mechanism is probably that erlotinib influence the corneal epithelium by inhibiting the EGFR activation.