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环境干燥性眼应激后小鼠角膜基质神经的改变。

Alterations of Murine Subbasal Corneal Nerves After Environmental Dry Eye Stress.

机构信息

Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

出版信息

Invest Ophthalmol Vis Sci. 2018 Apr 1;59(5):1986-1995. doi: 10.1167/iovs.17-23743.

Abstract

PURPOSE

To investigate the morphologic changes in the corneal subbasal nerve (CSN) plexus in wild-type mice after exposure to environmental dry eye stress (EDES) using in vivo confocal microscopy (IVCM).

METHODS

We examined 22 eyes of 8-week-old wild-type male mice (Balb/c, n = 11). The mice were exposed to an air fan inside a small compartment 5 hours/day for 3 days (EDES). Aqueous tear secretion and corneal epithelial damage were assessed. The CSNs were investigated by laser-scanning IVCM. Density; tortuosity; and reflectivity of CSNs; and dendritic cell (DC) densities were evaluated using semi-automated NeuronJ software.

RESULTS

EDES significantly decreased the aqueous tear secretion quantity (P = 0.0019) and significantly increased the corneal fluorescein (P = 0.005) and lissamine green staining scores (P = 0003). The CSN density showed a significant decrease after EDES exposure (before, 2813 ± 762 pixels/frame; after, 1906 ± 896 pixels/frame, P = 0.0071). The tortuosity and the reflectivity grades did not show statistically significant differences after EDES exposure (tortuosity, P = 0.307; reflectivity, P = 0.758). However, the mean DC density showed a significant increase after EDES exposure (before, 12.62 ± 5.94 cells/mm2; after, 15.93 ± 5.30 cells/mm2, P = 0.026).

CONCLUSIONS

Even short-term exposure to EDES induced alterations in the CSN plexus morphology including decreased subbasal corneal nerve density and increased amount of DCs in mice. The EDES mouse model is a promising model to study the ocular surface and corneal nerve changes associated with dry eye disease.

摘要

目的

使用活体共聚焦显微镜(IVCM)研究环境干燥眼应激(EDES)后野生型小鼠角膜基底神经丛(CSN)的形态变化。

方法

我们检查了 8 周龄野生型雄性小鼠(Balb/c,n=11)的 22 只眼睛。将小鼠暴露在小隔间内的空气扇中,每天 5 小时,持续 3 天(EDES)。评估泪液分泌和角膜上皮损伤。通过激光扫描 IVCM 研究 CSN。使用半自动 NeuronJ 软件评估 CSN 的密度、扭曲度和反射率;以及树突状细胞(DC)密度。

结果

EDES 显著降低了泪液分泌量(P=0.0019),并显著增加了角膜荧光素(P=0.005)和 Lissamine 绿染色评分(P=0.0003)。EDES 暴露后 CSN 密度显著降低(暴露前,2813±762 像素/帧;暴露后,1906±896 像素/帧,P=0.0071)。EDES 暴露后,CSN 的扭曲度和反射率等级没有统计学差异(扭曲度,P=0.307;反射率,P=0.758)。然而,EDES 暴露后平均 DC 密度显著增加(暴露前,12.62±5.94 个细胞/mm2;暴露后,15.93±5.30 个细胞/mm2,P=0.026)。

结论

即使是短期暴露于 EDES,也会导致 CSN 丛形态发生改变,包括小鼠角膜基底神经密度降低和 DC 数量增加。EDES 小鼠模型是研究与干眼症相关的眼表面和角膜神经变化的有前途的模型。

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