Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, United States.
https://orcid.org/0000-0002-1478-4200.
Invest Ophthalmol Vis Sci. 2024 May 1;65(5):21. doi: 10.1167/iovs.65.5.21.
Aging is a risk factor for dry eye. We sought to identify changes in the aged mouse corneal epithelial transcriptome and determine how age affects corneal sensitivity, re-epithelialization, and barrier reformation after corneal debridement.
Corneal epithelium of female C57BL/6J (B6) mice of different ages (2, 12, 18, and 24 months) was collected, RNA extracted, and bulk RNA sequencing performed. Cornea sensitivity was measured with an esthesiometer in 2- to 3-month-old, 12- to 13-month-old, 18- to 19-month-old, and 22- to 25-month-old female and male mice. The 2-month-old and 18-month-old female and male mice underwent unilateral corneal debridement using a blunt blade. Wound size and fluorescein staining were visualized and photographed at different time points, and a re-epithelialization rate curve was calculated.
There were 157 differentially expressed genes in aged mice compared with young mice. Several pathways downregulated with age control cell migration, proteoglycan synthesis, and collagen trimerization, assembly, biosynthesis, and degradation. Male mice had decreased corneal sensitivity compared with female mice at 12 and 24 months of age. Aged mice, irrespective of sex, had delayed corneal re-epithelialization in the first 48 hours and worse corneal fluorescein staining intensity at day 14 than young mice.
Aged corneal epithelium has an altered transcriptome. Aged mice regardless of sex heal more slowly and displayed more signs of corneal epithelial defects after wounding than young mice. These results indicate that aging significantly alters the corneal epithelium and its ability to coordinate healing.
衰老会增加干眼症的风险。我们试图确定老年小鼠角膜上皮转录组的变化，并确定年龄如何影响角膜敏感性、角膜再上皮化以及角膜清创后的屏障重建。
收集不同年龄（2、12、18 和 24 个月）的雌性 C57BL/6J（B6）小鼠的角膜上皮，提取 RNA 并进行批量 RNA 测序。使用触诊仪测量 2-3 个月、12-13 个月、18-19 个月和 22-25 个月大的雌性和雄性小鼠的角膜敏感性。2 个月和 18 个月大的雌性和雄性小鼠使用钝刀片进行单侧角膜清创。在不同时间点可视化和拍摄伤口大小和荧光素染色，并计算再上皮化率曲线。
与年轻小鼠相比，老年小鼠有 157 个差异表达基因。几个与年龄相关的下调通路控制着细胞迁移、蛋白聚糖合成以及胶原三聚体的组装、生物合成和降解。与 12 个月龄的雌性小鼠相比，12 个月龄的雄性小鼠的角膜敏感性降低。与年轻小鼠相比，无论性别如何，老年小鼠在前 48 小时的角膜再上皮化速度较慢，第 14 天的角膜荧光素染色强度更差。
老年角膜上皮具有改变的转录组。无论性别如何，老年小鼠的伤口愈合速度较慢，并且在受伤后比年轻小鼠表现出更多的角膜上皮缺陷迹象。这些结果表明，衰老会显著改变角膜上皮及其协调愈合的能力。
