Therapeutic efficacy of trehalose eye drops for treatment of murine dry eye induced by an intelligently controlled environmental system
Therapeutic efficacy of trehalose eye drops for treatment of murine dry eye induced by an intelligently controlled environmental system
复制标题
海藻糖滴眼液治疗智能控制环境系统所致小鼠干眼症的疗效
作者：
Shuai Shi;Guoting Liu;Christophe Baudouin;WeiChen
目的 确定二糖海藻糖 (TT) 滴眼液滴注是否可以减轻干眼小鼠模型的眼表损伤。方法 使用智能控制环境系统 (ICES) 诱导小鼠干眼。在没有局部治疗的情况下将小鼠圈养在 ICES 中 21 天后，将小鼠随机分为三组：三周不滴眼液 (ICES)，每天四次，双侧 PBS 0.01 M 10 µl/眼 (ICES+PBS)，或双侧 TT 87.6 mM 10 µl/眼 (ICES+TT)。另一组未暴露于 ICES 且未接受任何治疗的小鼠作为对照组 (UT)。使用俄勒冈绿葡聚糖（OGD）和荧光素染色评估每组的眼表完整性。通过对整个角膜进行免疫组织学分析来确定occludin、外皮蛋白和富含脯氨酸的小蛋白2的表达和分布。通过免疫组织学评估热休克蛋白 70 (HSP70) 和基质金属蛋白酶 9 (MMP-9) 的表达。通过结膜中白介素-1β (IL-1β)、IL-2、IL-6、IL-17 和肿瘤坏死因子-α 的实时 PCR 评估与每次治疗相关的眼表炎症。结果 ICES+TT 组角膜上皮 OGD 染色低于 ICES 和 ICES+PBS 组。 ICES+TT组的角膜上皮occludin染色明显比ICES和ICES+PBS组更均匀，并且没有脱落的顶端上皮细胞。整个角膜的外皮蛋白和富含脯氨酸的小蛋白 2 标记显示，与 ICES+TT 组相比，未接受治疗或 PBS 滴注的组中它们的表达上调。 HSP70 和 MMP-9 免疫标记显示，ICES 后角膜上皮表达显着增加。海藻糖处理组的 HSP70 和 MMP-9 表达谱与对照组 (UT) 相似。 ICES+TT 组的结膜 IL-1β、IL-2、IL-6、IL-17、肿瘤坏死因子-α (TNF-α) 和 MMP-9 mRNA 表达量低于 ICES 或 ICES+PBS 组。结论 海藻糖的应用可恢复干燥模型损伤的干眼小鼠的眼表完整性，抑制炎症和蛋白水解 MMP-9 和 HSP70 的表达以及角化。
Purpose To determine whether eye drop instillation of the disaccharide trehalose (TT) alleviates ocular surface damage in a dry eye murine model. Methods Dry eye was induced in mice using an intelligently controlled environmental system (ICES). After 21 days housed in the ICES without topical treatment, the mice were randomly divided into three groups: no eye drops (ICES) for three weeks, four times a day with PBS 0.01 M 10 µl/eye bilaterally (ICES+PBS), or with TT 87.6 mM 10 µl/eye bilaterally (ICES+TT). Another mice group that was not exposed to the ICES and received no treatment served as a control group (UT). The ocular surface integrity, in each group, was evaluated using Oregon Green dextran (OGD) and fluorescein staining. The expression and distribution of occludin, involucrin, and small proline-rich protein 2 were determined with immunohistology analysis on whole mounted corneas. Heat shock protein 70 (HSP70) and matrix metalloproteinase 9 (MMP-9) expression was estimated with immunohistology. Ocular surface inflammation associated with each treatment was estimated with real time-PCR of interleukin-1β (IL-1β), IL-2, IL-6, IL-17, and tumor necrosis factor-alpha in the conjunctiva. Results OGD staining in the cornea epithelium was lower in the ICES+TT group than in the ICES and ICES+PBS groups. Corneal epithelial occludin staining was markedly more homogenous in the ICES+TT group than in ICES and ICES+PBS groups, and there were no desquamating apical epithelial cells. Involucrin and small proline-rich protein 2 labeling of whole mounted corneas revealed upregulation of their expression in the groups, which received no treatment or PBS instillation compared to the ICES+TT group. HSP70 and MMP-9 immunolabeling revealed a marked increase in corneal epithelial expression in response to the ICES. The group treated with trehalose showed a similar profile expression of HSP70 and MMP-9 as the control group (UT). Conjunctival IL-1β, IL-2, IL-6, IL-17, tumor necrosis factor-alpha (TNF-α), and MMP-9 mRNA expression was lower in the ICES+TT group than in the ICES or ICES+PBS group. Conclusions Trehalose application restored ocular surface integrity, suppressed inflammatory and proteolytic MMP-9 and HSP70 expression, and keratinization in mice with dry eye damaged by a desiccative model.
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影响因子：
4.4
作者：
Chotikavanich S;de Paiva CS;Li de Q;Chen JJ;Bian F;Farley WJ;Pflugfelder SC
通讯作者：
Pflugfelder SC
DOI：
10.1034/j.1600-0420.1998.760113.x
发表时间：
1998-02
期刊：
Acta ophthalmologica Scandinavica
影响因子：
--
作者：
C. Paschides;M. Stefaniotou;J. Papageorgiou;P. Skourtis;K. Psilas
通讯作者：
C. Paschides;M. Stefaniotou;J. Papageorgiou;P. Skourtis;K. Psilas
DOI：
10.1007/s00417-011-1676-y
发表时间：
2011-08-01
影响因子：
2.7
作者：
Cejkova, Jitka;Ardan, Taras;Luyckx, Jacques
通讯作者：
Luyckx, Jacques
DOI：
10.1016/s0074-7696(08)61052-9
发表时间：
1999
期刊：
International review of cytology
影响因子：
--
作者：
K. Matter;M. Balda
通讯作者：
K. Matter;M. Balda
影响因子：
2.2
作者：
Thierry Pauloin;M. Dutot;F. Joly;J. Warnet;P. Rat
通讯作者：
Thierry Pauloin;M. Dutot;F. Joly;J. Warnet;P. Rat