[A preliminary study on the safety of berberine solution in rabbit eyes with topical application]

Objective: To study the safety of topical berberine solution in rabbit eyes and its effect on corneal epithelial repair in rabbit eyes. Methods: Experimental Study. Ninety-two Japanese rabbits were randomly divided into two groups by random number table method: the general group (32 rabbits, 64 eyes) and the corneal injury group (60 rabbits, 60 eyes).The general groups were further divided into 4 groups by random number table method, and each group has 8 rabbits (16 eyes). According to the administration of deionized water or 0.5, 1.0, 1.5 mg/ml berberine solution, they were divided into the general control group and the general A, B, and C group. Dosing with both eyes, each eye was given a single dose, and then it was given multiple times for 4 weeks after observation for 72h. After the corneal epithelium injury model made in the right eye of rabbits in the corneal injury groups, they were divided into a corneal injury control group and a corneal injury group A, B, and C according to the administration of deionized water or 0.5, 1.0, 1.5 mg/ml berberine solution. there were 5 rabbits (15 eyes) in each group, and the solutions were given continuously for 1 week. The rabbits in the general group were observed their behavioral changes, ocular surface and iris were scored by Draize eye irritation test scoring system. IOP was measured at different time points. Electroretinogram (ERG) was used to detect b-wave amplitude. In the corneal injury group, corneal epithelial defect repairment was observed at 1, 2, 3, 4, 5, 6, and 7 days after the corneal defect. Corneal histopathology observation after discontinuation of all rabbits. The pH value of rabbit tears was described by the paired t test, and the score of Draize eye irritation test were described by the rank-sum test. The analysis of variance and SNK-q were used for IOP, electroretinogram b-wave amplitude, corneal epithelial injury area and repair time. Results: No abnormal behavior was observed in the general group rabbits after single and multiple administration. There was no significant difference in the Draize eye irritation score among the general control group and the general group A, B, C at 1, 2, and 4 weeks of multiple administrations. Among them, the Draize eye irritation score of the general group C was 7 (0, 12), 6 (0, 10), 6 (0, 16) points (χ(2)=1.640, 0.265, 1.963, 1.381; P>0.05).There were no significant difference in IOP at different times among the general control group and the general group A, B, C at different times (F=0.065, 0.292, 0.015, 0.041; P>0.05). Before multiple administrations and after administration at 2, 4 weeks, the b-wave amplitudes of the general control group were (127.75±17.12), (129.18±15.83), (128.81±13.58) μV, and the general group A were (130.68).±18.75), (131.38±16.96), (130.62±12.18) μV,and the general group B were (128.00±16.74), (128.44±16.64), (129.06±16.16) μV, and the general group C were (131.81±19.37), (132.13±18.36), (129.94±12.60) μV. There was no statistically significant difference in b-wave amplitude in the groups at different times before and after administration (F=0.037, 0.011, 0.017, 0.702; P>0.05). There was no significant difference in the results of corneal histopathology among the general control group and the general group A, B, C. The area of corneal epithelial defect in each corneal injury group was statistically significant at different time (F=5.316, 25.864, 127.613; P<0.05). The corneal injury control group compared with the corneal injury group A, B, C, the corneal epithelial defect area in the corneal injury group C was significantly larger than the other three groups, with statistical differences (q=5.153, 10.313, 6.976; P<0.05). The repair time of corneal epithelial in control group and the group A,B,C of corneal injury were (83.0±1.85), (82.9±2.07), (83.7±2.09) and (101.6±2.20) h. The corneal epithelium defect repair time in group C was longer and the difference was statistically significant (F=301.437, P=0.000). Comparing the corneal injury control group and corneal injury group A and B, there was no statistical difference in the repair time of corneal epithelial defect (F=0.813, P=0.450). After repair, there was no significant difference in the pathological results of the corneal tissue between the corneal injury groups. Conclusions: Berberine solution in rabbit eyes with topical application was safety, and has no obvious toxic effect on the ocular surface and ERG of normal rabbits. 1.5 mg/ml berberine solution delayed the repair of experimental corneal epithelial defect, but had no effect on the integrity of corneal tissue after repair. (Chin J Ophthalmol, 2020, 56: 131-137).