Dynamic ocular surface and lacrimal gland changes induced in experimental murine dry eye.
Dynamic ocular surface and lacrimal gland changes induced in experimental murine dry eye.
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实验性小鼠干眼症引起的动态眼表和泪腺变化
DOI：
10.1371/journal.pone.0115333
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Xiao B;Wang Y;Reinach PS;Ren Y;Li J;Hua S;Lu H;Chen W
干眼病可能是Sjögren综合征中泪腺功能不全或泪膜蒸发增加的结果，尽管泪腺功能正常。为了确定这些模型中的严重程度效应与潜在的病理生理反应之间是否存在相关性，我们比较了在6周期间发生的每个参数的时间依赖性变化。采用智能控制环境系统（ICES）诱导6周龄雌性C57BL/6小鼠干眼。60只小鼠分别饲养1、2、4、6周。12只在正常环境下饲养，每日皮下注射氢溴酸东莨菪碱（SCOP） 3次，连续5天。另外60只老鼠被安置在正常环境中，没有接受任何治疗。角膜荧光素染色以及角膜MMP-9和caspase-3水平的测量与TUNEL试验同时进行。通过实时荧光定量PCR检测结膜和泪腺样本（LGs）的白细胞介素-17（IL-17）、IL-23、IL-6、IL-1、TNF-α、IFN-γ和TGF-β2水平。免疫组化及流式细胞术检测颈部淋巴结免疫细胞浸润情况。光镜和透射电镜研究评估了LGs细胞结构的变化。ICES诱导的角膜上皮破坏和凋亡在第2周达到峰值，并在随后的4周保持稳定。ICES组泪腺促炎细胞因子水平升高明显低于SCOP组。与较低的促炎细胞因子水平一致，ICES组泪腺胞质囊泡密度和大小均超过SCOP组。ICES和SCOP诱导的小鼠干眼效应在两周内逐渐加重。随后，病情在接下来的四周内趋于稳定。ICES在眼表引起局部效应，但未引起泪腺炎症和细胞结构改变，这是ICES模型中干眼严重程度低于SCOP模型的原因。
Dry eye disease can be a consequence of lacrimal gland insufficiency in Sjögren’s Syndrome or increased tear film evaporation despite normal lacrimal gland function. To determine if there is a correlation between severity effects in these models and underlying pathophysiological responses, we compared the time dependent changes in each of these parameters that occur during a 6 week period. Dry eye was induced in 6-week-old female C57BL/6 mice by exposing them to an Intelligently Controlled Environmental System (ICES). Sixty mice were housed in ICES for 1, 2, 4 and 6 weeks respectively. Twelve were raised in normal environment and received subcutaneous injections of scopolamine hydrobromide (SCOP) 3 times daily for 5 days. Another sixty mice were housed in a normal environment and received no treatment. Corneal fluorescein staining along with corneal MMP-9 and caspase-3 level measurements were performed in parallel with the TUNEL assay. Interleukin-17(IL-17), IL-23, IL-6, IL-1, TNF-α, IFN-γ and TGF-β2 levels were estimated by real-time PCR measurements of conjunctival and lacrimal gland samples (LGs). Immunohistochemistry of excised LGs along with flow cytometry in cervical lymph nodes evaluated immune cell infiltration. Light and transmission electron microscopy studies evaluated LGs cytoarchitectural changes. ICES induced corneal epithelial destruction and apoptosis peaked at 2 weeks and kept stable in the following 4 weeks. In the ICES group, lacrimal gland proinflammatory cytokine level increases were much lower than those in the SCOP group. In accord with the lower proinflammatory cytokine levels, in the ICES group, lacrimal gland cytosolic vesicular density and size exceeded that in the SCOP group. ICES and SCOP induced murine dry eye effects became progressively more severe over a two week period. Subsequently, the disease process stabilized for the next four weeks. ICES induced local effects in the ocular surface, but failed to elicit lacrimal gland inflammation and cytoarchitectural changes, which accounts for less dry eye severity in the ICES model than that in the SCOP model.
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影响因子：
4.5
作者：
Kang MH;Kim MK;Lee HJ;Lee HI;Wee WR;Lee JH
通讯作者：
Lee JH
影响因子：
--
作者：
FOX, RI;ROBINSON, CA;HOWELL, FV
通讯作者：
HOWELL, FV
影响因子：
3.4
作者：
Chen, Wei;Zhang, Xiaobo;Qu, Jia
通讯作者：
Qu, Jia
影响因子：
3.7
作者：
Kamoi M;Ogawa Y;Nakamura S;Dogru M;Nagai T;Obata H;Ito M;Kaido M;Kawakita T;Okada Y;Kawakami Y;Shimmura S;Tsubota K
通讯作者：
Tsubota K
DOI：
10.1084/jem.163.5.1037
发表时间：
1986-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kehrl JH;Wakefield LM;Roberts AB;Jakowlew S;Alvarez-Mon M;Derynck R;Sporn MB;Fauci AS
通讯作者：
Fauci AS