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衰老对小鼠角膜和眼表面稳态的影响。

The Effects of Aging on Corneal and Ocular Surface Homeostasis in Mice.

机构信息

Department of Optometry and Vision Sciences, University of Melbourne, Parkville, Victoria, Australia.

Neuroscience and Ophthalmology Research Group, Institute of Clinical Sciences, University of Birmingham, Birmingham, United Kingdom.

出版信息

Invest Ophthalmol Vis Sci. 2019 Jun 3;60(7):2705-2715. doi: 10.1167/iovs.19-26631.

Abstract

PURPOSE

Aging is a risk factor for dry eye disease. The aim of this study was to investigate if aging is associated with a range of signs of dry eye disease, including tear hyperosmolarity, reduced nerve density, and increased dendritic cell number, in mice.

METHOD

Healthy C57BL/6 female mice, aged 2 months (young, n = 10) and 22 months (aged, n = 11) were used. Clinical assessments included corneal sensitivity (Cochet-Bonnet esthesiometry), tear secretion (Phenol red thread test), tear film osmolarity (TearLab osmometer), and corneal thickness (optical coherence tomography). The sum length of the corneal superficial terminals and sub-basal nerves, density of vertical nerve projections, and density and tree area of resident epithelial dendritic cells, were assessed using immunofluorescence and confocal microscopy.

RESULTS

Aged mice had significantly higher tear secretion, lower corneal sensitivity, and a thicker corneal stroma but thinner epithelium. There was no significant intergroup difference for tear osmolarity. Aged mice showed a significantly lower sum length of nerves in the superficial terminals and sub-basal plexus, relative to young mice. Dendritic cell density and morphology were similar in both groups.

CONCLUSIONS

In mice, aging is associated with higher tear secretion and corneal epithelial thinning, together with lower corneal nerve density and sensitivity. However, aging was not significantly associated with changes to tear osmolarity or dendritic cell density or size, despite a significant reduction in total nerve length. These findings demonstrate that aged mice exhibit some changes to ocular surface parameters that parallel the anomalies evident in dry eye disease.

摘要

目的

衰老也是干眼症的一个风险因素。本研究旨在探究在小鼠中,衰老是否与干眼症的多种表现相关,包括泪液高渗、神经密度降低和树突状细胞数量增加。

方法

使用 2 月龄(年轻组,n=10)和 22 月龄(老年组,n=11)的健康 C57BL/6 雌性小鼠。临床评估包括角膜敏感性(Cochet-Bonnet 触诊仪)、泪液分泌(Phenol red 试纸试验)、泪膜渗透压(TearLab 渗透压仪)和角膜厚度(光学相干断层扫描)。使用免疫荧光和共聚焦显微镜评估角膜表面末梢和基底下神经的总长度、垂直神经投射密度以及常驻上皮树突状细胞的密度和树突面积。

结果

老年小鼠的泪液分泌显著增加,角膜敏感性显著降低,角膜基质变厚而上皮变薄。两组间泪液渗透压无显著差异。与年轻小鼠相比,老年小鼠的角膜表面末梢和基底下神经丛的总长度显著降低。两组间树突状细胞密度和形态无显著差异。

结论

在小鼠中,衰老与更高的泪液分泌和角膜上皮变薄有关,同时还伴有角膜神经密度和敏感性降低。然而,尽管总神经长度显著减少,衰老与泪液渗透压或树突状细胞密度或大小的变化并无明显相关性。这些发现表明,老年小鼠的眼部表面参数发生了一些变化,与干眼症中存在的异常相似。

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