Raghunathan VijayKrishna, Nartey Andrews, Dhamodaran Kamesh, Baidouri Hasna, Staverosky Julia A, Keller Kate E, Zientek Keith, Reddy Ashok, Acott Ted, Vranka Janice A
Department of Basic Sciences, College of Optometry, University of Houston, Houston, Texas.
Ophthalmology and Visual Sciences, Casey Eye Institute.
bioRxiv. 2023 Mar 12:2023.03.11.532242. doi: 10.1101/2023.03.11.532242.
Biophysical and biochemical attributes of the extracellular matrix are major determinants of cell fate in homeostasis and disease. Ocular hypertension and glaucoma are diseases where the trabecular meshwork tissue responsible for aqueous humor egress becomes stiffer accompanied by changes in its matrisome in a segmental manner with regions of high or low flow. Prior studies demonstrate these alterations in the matrix are dynamic in response to age and pressure changes. The underlying reason for segmentation or differential response to pressure and stiffening are unknown. This is largely due to a lack of appropriate models ( or ) to study this phenomena. In this study, we characterize the biomechanical attributes, matrisome, and incidence of crosslinks in the matrix deposited by primary cells isolated from segmental flow regions and when treated with glucocorticosteroid. Data demonstrate that matrix deposited by cells from low flow regions are stiffer and exhibit a greater number of immature and mature crosslinks, and that these are exacerbated in the presence of steroid. We also show a differential response of high or low flow cells to steroid via changes observed in the matrix composition. We conclude that although a mechanistic basis for matrix stiffness was undetermined in this study, it is a viable tool to study cell-matrix interactions and further our understanding of trabecular meshwork pathobiology.
细胞外基质的生物物理和生化特性是体内稳态和疾病中细胞命运的主要决定因素。高眼压症和青光眼是这样的疾病，即负责房水流出的小梁网组织会变得更硬，同时其基质组分会随着高流量或低流量区域呈节段性变化。先前的研究表明，基质中的这些改变会随着年龄和压力变化而动态变化。节段性变化或对压力及硬化的差异反应的根本原因尚不清楚。这主要是由于缺乏合适的模型（或 ）来研究这一现象。在本研究中，我们对从节段性血流区域分离的原代细胞所沉积的基质的生物力学特性、基质组分和交联发生率进行了表征，并观察了其在糖皮质激素处理后的变化。数据表明，低流量区域细胞所沉积的基质更硬，且表现出更多未成熟和成熟的交联，并且在存在类固醇的情况下这些情况会加剧。我们还通过观察到的基质组成变化展示了高流量或低流量细胞对类固醇的不同反应。我们得出结论，尽管本研究中基质硬度的机制基础尚未确定，但它是研究细胞 - 基质相互作用以及深化我们对小梁网病理生物学理解的一个可行工具。
