米索前列醇和环孢素 A 在小鼠干眼模型中治疗效果和耐受性的比较。
Comparison of Treatment Effect and Tolerance of the Topical Application of Mizoribine and Cyclosporine A in a Mouse Dry Eye Model.
机构信息
Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Xiamen University affiliated Xiamen Eye Center, Xiamen, Fujian, China.
出版信息
Transl Vis Sci Technol. 2020 Dec 15;9(13):22. doi: 10.1167/tvst.9.13.22. eCollection 2020 Dec.
PURPOSE
To compare the treatment effects and tolerability of a topical application of mizoribine (MZR) and cyclosporine A (CsA) eye drops (Restasis; Allergan, Inc., Irvine, CA, USA) in a mouse dry eye model.
METHODS
C57BL/6 mice subjected to desiccating stress (DS) were treated with 0.05% MZR in phosphate-buffered saline (PBS) or Restasis eye drops four times a day for 5 days. Untreated mice served as control. Tear secretion, Oregon green dextran staining, and the conjunctival goblet cell quantity were evaluated. The apoptosis and matrix metalloproteinase 9 (MMP-9) in the ocular surface, conjunctival CD4, and T helper-related cytokines were verified. The ocular tolerance of these two drugs was evaluated by observing the mice's behavioral changes.
RESULTS
Topical administrations of MZR or Restasis both increased tear production, maintained goblet cell density, and improved corneal barrier function. Both MZR and Restasis suppressed the expression of MMP-9 and apoptosis in the ocular surface. Meanwhile, both MZR and Restasis decreased the infiltration of CD4 T cells, reversed the production of interferon-γ, interleukin (IL)-17A, and IL-13 in conjunctiva under DS. The abovementioned efficacies between these two eye drops were not statistically significant. However, the number of scratching and wiping behaviors in the MZR-treated group was significantly less than in the Restasis-treated group.
CONCLUSIONS
MZR (0.05% in PBS) could be a good competitive product for Restasis because of the comparable treatment effect in dry eye diseases and better ocular tolerability in ocular itch and pain.
TRANSLATIONAL RELEVANCE
This study provided an immunosuppressive agent comparable to Restasis for the treatment of dry eye disease.
目的
比较咪康唑（MZR）和环孢素 A（CsA）眼药水（Restasis；Allergan，Inc.，Irvine，CA，USA）在小鼠干眼症模型中的治疗效果和耐受性。
方法
对干燥应激（DS）的 C57BL/6 小鼠用 0.05% MZR 磷酸盐缓冲盐水（PBS）或 Restasis 眼药水每天四次滴眼 5 天进行治疗。未治疗的小鼠作为对照。评估泪液分泌、Oregon green 葡聚糖染色和结膜杯状细胞数量。验证眼表的细胞凋亡和基质金属蛋白酶 9（MMP-9）、结膜 CD4 和 T 辅助相关细胞因子。通过观察小鼠的行为变化评估这两种药物的眼部耐受性。
结果
MZR 或 Restasis 的局部给药均增加了泪液分泌，维持了杯状细胞密度，并改善了角膜屏障功能。MZR 和 Restasis 均抑制了眼表的 MMP-9 和细胞凋亡表达。同时，MZR 和 Restasis 均减少了 DS 下结膜中 CD4 T 细胞的浸润，逆转了干扰素-γ、白细胞介素（IL）-17A 和 IL-13 在结膜中的产生。这两种眼药水的上述疗效没有统计学差异。然而，MZR 治疗组的抓挠和擦拭行为次数明显少于 Restasis 治疗组。
结论
由于在干眼症中的治疗效果相当，且眼部瘙痒和疼痛的耐受性更好，因此 0.05% PBS 中的 MZR 可能成为 Restasis 的一种良好的竞争产品。
翻译自
Liu L, Wu Z, Liu Y, Li H, Zhou Z, Zhang X, Wang Y, Zhang J, Li X. Comparison of the Efficacy and Tolerability of Topical MZR and CsA Eye Drops in a Mouse Dry Eye Model. Ocul Immunol Inflamm. 2023;31(3):520-536. doi:10.1080/09273948.2022.2126241
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