The long-term effect of tacrolimus on alkali burn-induced corneal neovascularization and inflammation surpasses that of anti-vascular endothelial growth factor.
The long-term effect of tacrolimus on alkali burn-induced corneal neovascularization and inflammation surpasses that of anti-vascular endothelial growth factor.
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DOI：
10.2147/dddt.s175297
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Yuan J
中科院分区：
文献类型：
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作者：
Chen L;Zhong J;Li S;Li W;Wang B;Deng Y;Yuan J
探讨他克莫司对碱烧伤诱导的角膜新生血管(NV)和炎症反应的影响，并与抗血管内皮生长因子(抗血管内皮细胞生长因子)进行比较。将84只Wistar大鼠随机分为3组，分别给予生理盐水或0.05%他克莫司(0.5 mg/m L)，每日4次，或结膜下注射抗血管内皮生长因子(0.5 mg/0.05 m L)。分别于伤后第3、7、14、28天检测角膜新生血管、混浊和上皮缺损、炎症状态、促炎细胞因子和血管生成细胞因子水平。与对照组相比，他克莫司在伤后第7、14、28天显著降低角膜NV，抗血管内皮生长因子抗体在各时间点均显著降低角膜NV。然而，在第14天和第28天，他克莫司组的角膜新生血管数明显少于抗血管内皮生长因子组。此外，他克莫司和抗血管内皮生长因子抗体在第7天和第14天均可显著降低血管内皮细胞生长因子-A的表达，但两组间无显著差异。此外，他克莫司还能减轻角膜炎症反应，减少角膜混浊和角膜上皮缺损。他克莫司还能显著降低IL-1β、IL-6、单核细胞趋化蛋白-1、巨噬细胞炎性蛋白-1α和转化生长因子-β的表达。结果表明，0.05%他克莫司混悬液能有效地减轻碱烧伤所致的角膜新生血管和炎症反应，其效果优于第14天和第28天的结膜下注射抗血管内皮生长因子。
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). 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. 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. 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.