Cornea and External Disease, Department of Ophthalmology, University of South Florida, Morsani College of Medicine, Tampa, Florida.
Biomedical Atomic Force Microscopy Laboratory, Department of Biomedical Engineering, College of Engineering, University of Miami, Miami, Florida.
Am J Pathol. 2021 Dec;191(12):2184-2194. doi: 10.1016/j.ajpath.2021.08.016. Epub 2021 Sep 21.
Collagen XIV is poorly characterized in the body, and the current knowledge of its function in the cornea is limited. The aim of the current study was to elucidate the role(s) of collagen XIV in regulating corneal stromal structure and function. Analysis of collagen XIV expression, temporal and spatial, was performed at different postnatal days (Ps) in wild-type C57BL/6 mouse corneal stromas and after injury. Conventional collagen XIV null mice were used to inquire the roles that collagen XIV plays in fibrillogenesis, fibril packing, and tissue mechanics. Fibril assembly and packing as well as stromal organization were evaluated using transmission electron microscopy and second harmonic generation microscopy. Atomic force microscopy was used to assess stromal stiffness. Col14a1 mRNA expression was present at P4 to P10 and decreased at P30. No immunoreactivity was noted at P150. Abnormal collagen fibril assembly with a shift toward larger-diameter fibrils and increased interfibrillar spacing in the absence of collagen XIV was found. Second harmonic generation microscopy showed impaired fibrillogenesis in the collagen XIV null stroma. Mechanical testing suggested that collagen XIV confers stiffness to stromal tissue. Expression of collagen XIV is up-regulated following injury. This study indicates that collagen XIV plays a regulatory role in corneal development and in the function of the adult cornea. The expression of collagen XIV is recapitulated during wound healing.
胶原蛋白 XIV 在体内的特征描述较差，目前对其在角膜中的功能知之甚少。本研究旨在阐明胶原蛋白 XIV 在调节角膜基质结构和功能中的作用。在野生型 C57BL/6 小鼠角膜基质的不同出生后天数 (Ps) 和损伤后，分析胶原蛋白 XIV 的表达、时空特征。使用传统的胶原蛋白 XIV 缺失小鼠来探究胶原蛋白 XIV 在原纤维形成、原纤维包装和组织力学中的作用。使用透射电子显微镜和二次谐波产生显微镜评估原纤维组装和包装以及基质组织。使用原子力显微镜评估基质硬度。Col14a1 mRNA 表达在 P4 到 P10 时存在，在 P30 时减少。在 P150 时没有免疫反应性。在缺乏胶原蛋白 XIV 的情况下，发现胶原纤维的异常组装，向更大直径的纤维转移，并且纤维间间距增加。二次谐波产生显微镜显示胶原蛋白 XIV 缺失基质中原纤维形成受损。力学测试表明胶原蛋白 XIV 赋予基质组织硬度。胶原蛋白 XIV 的表达在损伤后上调。本研究表明胶原蛋白 XIV 在角膜发育和成年角膜功能中发挥调节作用。胶原蛋白 XIV 的表达在伤口愈合过程中被重新表达。
