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他克莫司对碱烧伤诱导的角膜新生血管形成和炎症的长期影响超过抗血管内皮生长因子。

The long-term effect of tacrolimus on alkali burn-induced corneal neovascularization and inflammation surpasses that of anti-vascular endothelial growth factor.

作者信息

Chen Ling, Zhong Jing, Li Saiqun, Li Weihua, Wang Bowen, Deng Yuqing, Yuan Jin

机构信息

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China,

出版信息

Drug Des Devel Ther. 2018 Sep 12;12:2959-2969. doi: 10.2147/DDDT.S175297. eCollection 2018.

Abstract

PURPOSE

To investigate the effect of tacrolimus in alkali burn-induced corneal neovascularization (NV) and inflammation and to compare with anti-vascular endothelial growth factor (anti-VEGF).

METHODS

After corneal alkali-burn, 84 Wistar rats were randomly divided into three groups and received either saline solution or 0.05% tacrolimus (0.5 mg/mL) four times daily, or subconjunctival anti-VEGF injection (0.5 mg/0.05 mL). Corneal NV, opacity and epithelial defects, the status of inflammation, and the levels of proinflammatory and angiogenic cytokines were assessed on Days 3, 7, 14 and 28 post-injury.

RESULTS

Compared with the control, tacrolimus significantly reduced corneal NV on Days 7, 14 and 28 post-injury, and anti-VEGF significantly reduced corneal NV at each assessment. Nevertheless, the tacrolimus group had significantly less corneal NV than the anti-VEGF group on Days 14 and 28. Furthermore, both tacrolimus and anti-VEGF significantly decreased the VEGF-A expression on Days 7 and 14, with no significant difference between the two groups. Moreover, corneal inflammatory response was alleviated, and corneal opacity and epithelial defects were significantly reduced by tacrolimus. Additionally, the expression of IL-1β, IL-6, monocyte chemotactic protein-1, macrophage inflammatory protein-1α and TGF-β were significantly decreased by tacrolimus.

CONCLUSION

Our findings suggested that 0.05% tacrolimus suspension eye drops effectively reduced alkali burn-induced corneal NV and inflammation, with a better effect than subconjunctival anti-VEGF injections on Days 14 and 28.

摘要

目的

研究他克莫司对碱烧伤诱导的角膜新生血管化(NV)和炎症的影响,并与抗血管内皮生长因子(抗VEGF)进行比较。

方法

角膜碱烧伤后,将84只Wistar大鼠随机分为三组,分别每日四次给予生理盐水或0.05%他克莫司(0.5mg/mL),或结膜下注射抗VEGF(0.5mg/0.05mL)。在损伤后第3、7、14和28天评估角膜NV、混浊度和上皮缺损、炎症状态以及促炎和血管生成细胞因子水平。

结果

与对照组相比,他克莫司在损伤后第7、14和28天显著减少角膜NV,抗VEGF在每次评估时均显著减少角膜NV。然而,在第14和28天,他克莫司组的角膜NV明显少于抗VEGF组。此外,他克莫司和抗VEGF在第7和14天均显著降低VEGF-A表达,两组之间无显著差异。此外,他克莫司减轻了角膜炎症反应,显著减少了角膜混浊度和上皮缺损。此外,他克莫司显著降低了IL-1β、IL-6、单核细胞趋化蛋白-1、巨噬细胞炎性蛋白-1α和TGF-β的表达。

结论

我们的研究结果表明,0.05%他克莫司混悬滴眼液可有效减少碱烧伤诱导的角膜NV和炎症,在第14和28天比结膜下注射抗VEGF效果更好。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/321f/6140698/17b278a961d2/dddt-12-2959Fig1.jpg

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