Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 315 Ferst Dr. NW, Atlanta, GA, 30332, USA.
Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland.
Ann Biomed Eng. 2018 Feb;46(2):365-374. doi: 10.1007/s10439-017-1967-5. Epub 2017 Nov 27.
Glaucoma is a common optic neuropathy characterized by retinal ganglion cell death. Elevated intraocular pressure (IOP), a key risk factor for glaucoma, leads to significant biomechanical deformation of optic nerve head (ONH) cells and tissues. ONH astrocytes respond to this deformation by transforming to a reactive, proliferative phenotype, which has been implicated in the progression of glaucomatous vision loss. However, little is known about the mechanisms of this transformation. In this study, we developed a 3D collagen gel culture system to mimic features of ONH deformation due to elevated IOP. Compressive loading of astrocyte-seeded collagen gels led to cell alignment perpendicular to the direction of strain, and increased astrocyte activation, as assayed by GFAP, vimentin, and s100β levels, as well as MMP activity. This proof-of-concept study shows that this system has potential for studying mechanisms of astrocyte mechanobiology as related to the pathogenesis of glaucoma. Further work is needed to establish the possible interplay of mechanical stimulation, matrix properties, and hypoxia on the observed response of astrocytes.
青光眼是一种常见的视神经病变，其特征是视网膜神经节细胞死亡。眼内压升高（IOP）是青光眼的一个关键危险因素，它导致视神经盘（ONH）细胞和组织发生显著的生物力学变形。ONH 星形胶质细胞通过转化为反应性、增殖性表型来应对这种变形，这与青光眼视力丧失的进展有关。然而，目前对于这种转化的机制知之甚少。在这项研究中，我们开发了一种 3D 胶原凝胶培养系统，以模拟由于眼内压升高导致的 ONH 变形的特征。用压缩力加载星形胶质细胞种子胶原凝胶会导致细胞沿应变方向垂直排列，并增加星形胶质细胞的激活，如 GFAP、波形蛋白和 s100β 水平以及 MMP 活性的测定。这项概念验证研究表明，该系统具有研究与青光眼发病机制相关的星形胶质细胞机械生物学机制的潜力。需要进一步的工作来确定机械刺激、基质特性和缺氧对星形胶质细胞观察到的反应的可能相互作用。
