眼科学报2024，Vol.39Issue(10)：489-500,12.DOI:10.12419/24071007
托珠单抗调控角膜碱烧伤后修复的研究
Study on the regulation of tocilizumab on corneal repair after alkali burns
摘要
Abstract
Objective:To evaluate the safety and effect of topical IL-6 inhibitor tocilizumab eye drops in regulating corneal alkali burn repair.Methods:Six mice without corneal burns were locally treated with tocilizumab eye drops(2.5 mg/mL)and six mice with corneal pseudo burn were treated with saline,respectively,as experimental and blank groups to evaluate the safety of tocilizumab eye drops.30 alkali burned mice were randomly divided into a treatment group and a control group in a 1:1 ratio.The treatment group received tocilizumab eye drops,while the control group received physiological saline solution 6 times per day for 14 days.Observe the anterior adhesion of the iris,detachment of the Descemet membrane,and corneal edema through anterior segment optical coherence tomography(AS-OCT),and examine corneal scarring and epithelial wound healing under a stereomicroscope.Evaluate IL-6 localization,myofibroblasts,immune cell infiltration,and corneal epithelial metaplasia on corneal sections.Evaluate corneal neovascularization and neovascularization area by whole-mount cornea staining.Detect the expression level of IL-6 in mouse cornea by qRT-PCR.Results:No significant damage to the corneal structure was observed in the treatment of unburned corneas with tocilizumab.After corneal alkali burns,the corneal structure was damaged,corneal scarring was formed,and delayed healing of corneal epithelial wounds was observed.After treatment with tocilizumab,the incidence of anterior synechia of the iris significantly decreased from 86.67%to 20%(P<0.01),the incidence of Descemet membrane detachment decreased from 93.33%to 53.33%(P<0.05),the corneal thickness was significantly less than that of the control group(100.03±15.73)μm vs.(207.02±56.30 μm)(P<0.001),the corneal opacity score decreased from 3.76±0.44 in the control group to 1.94±0.83 in the treatment group(P<0.001),and the epithelial healing rate in the treatment group was significantly higher than that in the control group on day 5(P<0.05),day 10(P<0.001),and day 14(P<0.001).After corneal alkali burns,IL-6 was distributed throughout the corneal layer,and a large number of myofibroblasts and immune cells were observed.After treatment with tocilizumab,the expression of IL-6 was inhibited(decreased by 77.5%,P<0.05),the number of myofibroblasts decreased from(91.44±65.60)per field to(12.89±10.51)per field(P<0.01),and the number of immune cells decreased from(60.30±28.71 cells)per field to 6.80±3.82 cells per field(P<0.001).In addition,tocilizumab also reduced the number of goblet cells per field in corneal sections(from 11.30±5.29 to 2.00±1.90)(P<0.01),and reduced the formation of corneal neovascularization and neovascular lymphatic vessels(by 76.86%and 71.16%,respectively,both P<0.001).Conclusion:Topical use of tocilizumab to inhibit IL-6 showed no significant corneal toxicity and can regulate the repair of cornea after alkali burns.关键词
角膜碱烧伤/白介素-6/托珠单抗Key words
corneal alkali burn/interleukin-6/tocilizumab分类
医药卫生引用本文复制引用
张祺恩,王佳琦,何嘉瑜,卓晴晴,袁钊辉..托珠单抗调控角膜碱烧伤后修复的研究[J].眼科学报,2024,39(10):489-500,12.基金项目
广州市科技项目(202102080039).This work was supported by grants from the Science and Technology Project of Guangzhou Municipal(202102080039). （202102080039）
