Comparison of Treatment Effect and Tolerance of the Topical Application of Mizoribine and Cyclosporine A in a Mouse Dry Eye Model.
Comparison of Treatment Effect and Tolerance of the Topical Application of Mizoribine and Cyclosporine A in a Mouse Dry Eye Model.
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局部应用咪唑立宾和环孢素A在小鼠干眼模型中的治疗效果和耐受性比较
DOI：
10.1167/tvst.9.13.22
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发表时间：
2020-12
影响因子：
3
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Lin X;Wu Y;Tang L;Ouyang W;Yang Y;Liu Z;Wu J;Zheng X;Huang C;Zhou Y;Zhang X;Chen Y;Li W;Hu J;Liu Z
比较咪唑立宾（MZR）和环孢菌素A（CsA）滴眼液（Restasis; Allergan，Inc.，Irvine，CA，USA）在小鼠干眼模型中进行。方法C57 BL/6小鼠在干燥应激（DS）状态下，分别给予0.05%MZR磷酸盐缓冲液（PBS）和Restasis滴眼液，每天4次，连续5d。未处理的小鼠作为对照。评价泪液分泌、俄勒冈州绿色葡聚糖染色和结膜杯状细胞数量。检测眼表细胞凋亡、基质金属蛋白酶9（MMP-9）表达、结膜CD 4表达及T辅助细胞相关细胞因子表达。通过观察小鼠行为学变化评价两种药物的眼耐受性。结果局部应用MZR或Restasis均能增加泪液分泌，维持杯状细胞密度，改善角膜屏障功能。MZR和Restasis均抑制眼表MMP-9的表达和细胞凋亡。同时，MZR和Restasis均能减少DS下结膜中CD 4 + T细胞的浸润，逆转IFN-γ、IL-17 A和IL-13的产生。两种滴眼液的疗效差异无统计学意义。然而，MZR给药组的抓挠和擦拭行为次数显著少于Restesis给药组。结论MZR（0.05% PBS溶液）对干眼症的治疗效果相当，对眼部瘙痒和疼痛的眼部耐受性更好，是Restasis的一个很好的竞争产品。翻译相关性本研究提供了一种与Restasis相当的免疫抑制剂，用于治疗干眼病。
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.
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影响因子：
13.7
作者：
Kaçmaz RO;Kempen JH;Newcomb C;Daniel E;Gangaputra S;Nussenblatt RB;Rosenbaum JT;Suhler EB;Thorne JE;Jabs DA;Levy-Clarke GA;Foster CS
通讯作者：
Foster CS
影响因子：
8
作者：
Kang H;Cha KH;Cho W;Park J;Park HJ;Sun BK;Hyun SM;Hwang SJ
通讯作者：
Hwang SJ
影响因子：
13.7
作者：
Sall, K;Stevenson, OD;Reis, BL
通讯作者：
Reis, BL
小鼠瘙痒与疼痛之间的行为分化。
影响因子：
7.4
作者：
Shimada SG;LaMotte RH
通讯作者：
LaMotte RH
影响因子：
10.8
作者：
Gupta, Chhavi;Chauhan, Anuj
通讯作者：
Chauhan, Anuj