局部脂联素治疗干燥应激诱导的干眼小鼠模型的疗效。

Therapeutic effect of topical adiponectin in a mouse model of desiccating stress-induced dry eye.

机构信息

Department of Ophthalmology and Research Institute of Medical Sciences, Chonnam National University Medical School and Hospital, Gwangju, Korea.

出版信息

Invest Ophthalmol Vis Sci. 2013 Jan 7;54(1):155-62. doi: 10.1167/iovs.12-10648.

DOI:10.1167/iovs.12-10648

PMID:23211823

Abstract

PURPOSE

To investigate the therapeutic effect of topical adiponectin in a mouse model of experimental dry eye (EDE).

METHODS

EDE was created by desiccating stress in 6- to 8-week old female C57BL/6 mice. Eye drops consisting of 0.0001%, 0.001%, or 0.01% adiponectin, or balanced salt solution (BSS), were applied in EDE. Tear volume and corneal irregularity score were measured at 5 and 10 days after treatment. Levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and monokine induced by interferon-γ (MIG) were measured in the conjunctiva and lacrimal gland using a multiplex immunobead assay at 10 days. Periodic acid-Schiff staining, immunohistochemistry, and flow cytometry were also performed.

RESULTS

Mice treated with 0.001% or 0.01% adiponectin showed a significant improvement in tear volume and corneal irregularity compared with the EDE control and BSS-treated groups. A significant decrease in the levels of IL-1β, IL-6, TNF-α, IFN-γ, and MIG and staining intensity of TNF-α was observed in the 0.001% and 0.01% adiponectin-treated groups, compared with the other groups, in the conjunctiva and lacrimal gland. In the 0.001% and 0.01% adiponectin-treated groups, the density of conjunctival goblet cells was higher and the number of CD4+CXCR3+ T cells was lower than in the other groups. However, there were no significant differences in all parameters between the 0.0001% adiponectin and control groups.

CONCLUSIONS

Topical application of adiponectin can markedly improve clinical signs and decrease inflammation in the ocular surface and lacrimal gland of EDE, suggesting that adiponectin eye drops may be used as a therapeutic agent for dry eye disease.

摘要

目的

研究局部应用脂联素对实验性干眼（EDE）小鼠模型的治疗效果。

方法

通过 6-8 周龄雌性 C57BL/6 小鼠的干燥应激建立 EDE。在 EDE 治疗后 5 天和 10 天，应用含有 0.0001%、0.001%或 0.01%脂联素或平衡盐溶液（BSS）的眼药水。在治疗后 10 天，通过多重免疫珠测定法测量结膜和泪腺中白细胞介素（IL）-1β、IL-6、肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ和干扰素诱导的单克隆炎症因子（MIG）的水平。还进行了过碘酸-希夫染色、免疫组织化学和流式细胞术。

结果

与 EDE 对照组和 BSS 治疗组相比，用 0.001%或 0.01%脂联素治疗的小鼠的泪液体积和角膜不规则性明显改善。与其他组相比，在结膜和泪腺中观察到 0.001%和 0.01%脂联素治疗组的 IL-1β、IL-6、TNF-α、IFN-γ和 MIG 水平以及 TNF-α染色强度显著降低。在 0.001%和 0.01%脂联素治疗组中，结膜杯状细胞的密度较高，CD4+CXCR3+T 细胞的数量较低。然而，在 0.0001%脂联素与对照组之间，所有参数均无显著差异。