Inomata Takenori, Mashaghi Alireza, Hong Jiaxu, Nakao Takeshi, Dana Reza
Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA, United States of America.
Juntendo University Faculty of Medicine, Department of Ophthalmology, Tokyo, Japan.
PLoS One. 2017 Oct 6;12(10):e0185694. doi: 10.1371/journal.pone.0185694. eCollection 2017.
Corneal thickness is tightly regulated by its boundary endothelial and epithelial layers. The regulated set-point of corneal thickness likely shows inter-individual variations, changes by age, and response to stress. Using anterior segment-optical coherence tomography, we measure murine central corneal thickness and report on body size scaling of murine central corneal thickness during aging. For aged-matched mice, we find that corneal thickness depends on sex and strain. To shed mechanistic insights into these anatomical changes, we measure epithelial layer integrity and endothelial cell density during the life span of the mice using corneal fluorescein staining and in vivo confocal microscopy, respectively and compare their trends with that of the corneal thickness. Cornea thickness increases initially (1 month: 114.7 ± 3.0 μm, 6 months: 126.3 ± 1.6 μm), reaches a maximum (9 months: 129.3 ± 4.4 μm) and then reduces (12 months: 127 ± 2.9 μm, 13 months: 119.5 ± 7.6 μm, 14 months: 110.6 ± 10.6 μm), while the body size (weight) increases with age. We find that endothelial cell density reduces from 2 months old to 8 months old as the mice age and epithelial layer accumulates damages within this time frame. Finally, we compare murine corneal thickness with those of several other mammals including humans and show that corneal thickness has an allometric scaling with body size. Our results have relevance for organ size regulation, translational pharmacology, and veterinary medicine.
角膜厚度受到其边界内皮和上皮层的严格调控。角膜厚度的调控设定点可能存在个体差异、随年龄变化以及对应激的反应。我们使用眼前节光学相干断层扫描技术测量小鼠中央角膜厚度，并报告衰老过程中小鼠中央角膜厚度与体型的比例关系。对于年龄匹配的小鼠，我们发现角膜厚度取决于性别和品系。为了深入了解这些解剖学变化的机制，我们分别使用角膜荧光素染色和体内共聚焦显微镜在小鼠的生命周期内测量上皮层完整性和内皮细胞密度，并将它们的变化趋势与角膜厚度的变化趋势进行比较。角膜厚度最初增加（1个月：114.7±3.0μm，6个月：126.3±1.6μm），达到最大值（9个月：129.3±4.4μm），然后减小（12个月：127±2.9μm，13个月：119.5±7.6μm，14个月：110.6±10.6μm），而体型（体重）随年龄增加。我们发现随着小鼠年龄增长，内皮细胞密度从2个月大到8个月大逐渐降低，并且上皮层在此时间段内积累损伤。最后，我们将小鼠角膜厚度与包括人类在内的其他几种哺乳动物的角膜厚度进行比较，结果表明角膜厚度与体型存在异速生长比例关系。我们的研究结果对器官大小调控、转化药理学和兽医学具有重要意义。
