The Effects of Aging on Corneal and Ocular Surface Homeostasis in Mice
The Effects of Aging on Corneal and Ocular Surface Homeostasis in Mice
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DOI：
10.1167/iovs.19-26631
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发表时间：
2019-06-01
影响因子：
4.4
通讯作者：
Chinnery, Holly R.
中科院分区：
文献类型：
--
作者：
De Silva, Manikkuwadura Eranda Harshan;Hill, Lisa J.;Chinnery, Holly R.
目的.年龄是干眼病的一个危险因素。本研究的目的是调查衰老是否与干眼症的一系列体征有关，包括泪液高渗、神经密度降低和树突状细胞数量增加。使用2月龄（年轻，n = 10）和22月龄（老年，n = 11）的健康C57 BL/6雌性小鼠。临床评估包括角膜敏感性（Cochet-Bonnet触觉测量法）、泪液分泌（苯酚红线测试）、泪膜渗透压（TearLab渗透压计）和角膜厚度（光学相干断层扫描）。角膜表面末梢和基底下神经的总长度、垂直神经投射的密度、以及常驻上皮树突状细胞的密度和树面积使用免疫荧光和共聚焦显微镜进行评估。老年小鼠泪液分泌明显增加，角膜敏感性降低，角膜基质较厚，但上皮较薄。泪液渗透压无显著组间差异。老年小鼠表现出显着较低的总长度的神经在浅终末和亚基底神经丛，相对于年轻的小鼠。两组树突状细胞密度和形态相似。在小鼠中，衰老与更高的泪液分泌和角膜上皮变薄，以及更低的角膜神经密度和敏感性有关。然而，老化与泪液渗透压或树突状细胞密度或大小的变化无显著相关性，尽管总神经长度显著减少。这些发现表明，老年小鼠表现出一些眼表参数的变化，这些变化与干眼病中明显的异常平行。
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.