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Chinese Journal of Ophthalmologic Medicine(Electronic Edition) ›› 2020, Vol. 10 ›› Issue (04): 219-225. doi: 10.3877/cma.j.issn.2095-2007.2020.04.005

• Original Article • Previous Articles     Next Articles

Effect of tyrosine kinase inhibitor E7080 on laser induced choroidal neovascularization in rat

jingxue Zhang1, Xuejing Yan1, Qian Liu1, Shen Wu1,()   

  1. 1. Beijing Tongren Eye Cener, Beijing Tongren Hospital, Capital Medical University, Beijing Institute of Ophthalmology, Beijing Ophthalmology & Visual Sciences Key Lab., Beijing 100730, China
  • Received:2020-08-06 Online:2020-08-28 Published:2021-11-12
  • Contact: Shen Wu

Abstract:

Objective

The aim of this study was to expolre the effect of tyrosine kinase inhibitor E7080 on laser-induced choroidal neovascularization in rats.

Methods

Sixty adult male brown Norway rats were provided by Beijing Vital River Laboratory Animal Technology Co. Ltd. They were randomly divided into control group, E7080 low-dose (10 mg·kg-1·d-1) group, and E7080 high-dose (20 mg·kg-1·d-1) group according to random number table. The choroidal neovascularization was induced by fundus laser photocoagulation. The drug was applied at seven days after laser photocoagulation. Fundus fluorescein angiography was used to check choroidal neovascularization formation and fluorescence leakage at 7 days after laser photocoagulation, 7 days and 14 days after drug administration. The histology of choroidal neovascularization was assessed by histopathological examination at 7 days and 14 days after administration. The area of choroidal neovascularization was observed by staining isolectin B4 on RPE-choroid-sclera flat mounts. The CNV fluorescence signal intensity, thickness and CNV area stained with lectin B4s were statistically described as mean±standard deviation (Mean±SD). The comparison of the mean between different groups among multiple samples adopts repeated measures analysis of variance, and LSD test was used for pairwise comparison.

Results

FFA showed that after 7 days of administration, the relative leakage fluorescence signal intensity of CNV in the low-dose group and the high-dose group were (0.5378±0.0967) and (0.3774±0.086) respectively, which were lower than those of the control group (0.6752±0.095); the difference was statistically significant (t=6.342, 13.99; P<0.05); 14 days after administration, the relative leakage fluorescence signal intensity of CNV in the low-dose group and the high-dose group were (0.5735±0.0726), (0.4071±0.1197), also lower than the control group (0.7305±0.0924); the difference was statistically significant (t=6.92, 14.5; P<0.05). The results of hematoxylin-eosin staining showed that after 7 days of drug treatment, the CNV thickness of the low-dose group and the high-dose group were (84.14±8.829) μm and (77.23±9.365) μm, respectively, which were lower than those of the control group (125.3±18.18) μm; the difference was statistically significant (t=7.38, 8.628; P<0.05); 14 days after drug treatment, the CNV thickness of the low-dose group and the high-dose group were (86.21±10.51) μm and (77.88±7.39) μm, respectively , which were lower than those of the control group (147.9±19.66) μm; the difference is statistically significant (t=9.656, 10.44; P<0.05). Fluorescence staining of the RPE-choroid-sclera flat mounts showed that the average area of choroidal neovascularization in the low-dose group and high-dose group were (18 991±8665) μm2 and (20 083±11759) μm2, respectively, which were lower than those of the control group (51 156± 24348) μm2; the difference was statistically significant (t= 6.039, 6.593; P<0.05), and there was no significant difference between the low-dose group and high-dose group (t=0.2174, P>0.05).

Conclusions

The tyrosine kinase inhibitor E7080 could inhibit laser-induced choroidal neovascularization and related pathological damage through oral administration in rats.

Key words: Choroidal neovascularization, Tyrosine kinase inhibitor, Small molecule drug, Exudative age-related macular degeneration

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