Department of Anatomy and Regenerative Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA.
Department of Ophthalmology, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA.
Int J Mol Sci. 2020 Jul 21;21(14):5172. doi: 10.3390/ijms21145172.
Aging impacts the ocular surface and reduces intraepithelial corneal nerve (ICN) density in male and female mice. Many researchers use retired breeders to study naturally aged female mice. Yet, the impact of parity and the length of time since breeders were retired on age-related changes in the intraepithelial corneal nerves is not known. Here we study 2 month (M) nulliparous (NP) females as well as 9M, 10M, and 11M NP and multiparous (MP) female mice to determine whether parity impacts the age-related decline seen in corneal axon density; 9M male mice are also included in these assessments. After showing that parity attenuates age-related loss in axon density, we also assess the impact of parity on corneal epithelial cell proliferation and find that it impacts cell proliferation and axon density normalized by cell proliferation. Stromal nerve arborization is also impacted by aging with parity enhancing stromal nerves in older mice. qPCR was performed on 20 genes implicated in ICN density using corneal epithelial RNA isolated from 10M NP and MP mice and showed that NGF expression was significantly elevated in MP corneal epithelium. Corneal sensitivity was significantly higher in 9M MP mice compared to NP mice and increased sensitivity in MP mice was accompanied by increased nerve terminals in the apical and middle cell layers. Together, these data show that parity in mice attenuates several aspects of the age-related decline seen on the ocular surface by retaining sensory axons and corneal sensitivity as mice age.
衰老是影响眼表的一个重要因素，它会降低雄性和雌性小鼠的上皮内角膜神经（ICN）密度。许多研究人员使用退休的繁殖者来研究自然衰老的雌性小鼠。然而，关于繁殖者退休后的产仔次数和时间长短对与年龄相关的角膜上皮神经内变化的影响还不得而知。在这里，我们研究了 2 月龄（M）未产仔（NP）雌性以及 9M、10M 和 11M NP 和多产仔（MP）雌性小鼠，以确定产仔次数是否会影响角膜轴突密度的与年龄相关的下降；还包括了 9M 雄性小鼠的评估。在表明产仔次数可以减轻与年龄相关的轴突密度损失后，我们还评估了产仔次数对角膜上皮细胞增殖的影响，发现它会影响通过细胞增殖归一化的细胞增殖和轴突密度。基质神经分支也受到年龄的影响，产仔次数会增强老年小鼠的基质神经。使用从 10M NP 和 MP 小鼠的角膜上皮 RNA 进行了 20 个与 ICN 密度相关基因的 qPCR，结果表明 MP 角膜上皮中的 NGF 表达显著升高。与 NP 小鼠相比，9M MP 小鼠的角膜敏感性显著升高，并且 MP 小鼠的敏感性增加伴随着中、上层细胞中的神经末梢增加。综上所述，这些数据表明，产仔次数可以通过保留感觉轴突和角膜敏感性来减轻小鼠衰老时眼表出现的与年龄相关的多种下降。
