Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, United States; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States.
Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, United States; Department of Biomedical Engineering, University of Mississippi, MS, United States; Department of Mechanical Engineering, University of Mississippi, MS, United States.
Exp Eye Res. 2023 May;230:109446. doi: 10.1016/j.exer.2023.109446. Epub 2023 Mar 18.
Collagen is the main load-bearing component of cornea and sclera. When stretched, both of these tissues exhibit a behavior known as collagen fiber recruitment. In recruitment, as the tissues stretch the constitutive collagen fibers lose their natural waviness, progressively straightening. Recruited, straight, fibers bear substantially more mechanical load than non-recruited, wavy, fibers. As such, the process of recruitment underlies the well-established nonlinear macroscopic behavior of the corneoscleral shell. Recruitment has an interesting implication: when recruitment is incomplete, only a fraction of the collagen fibers is actually contributing to bear the loads, with the rest remaining "in reserve". In other words, at a given intraocular pressure (IOP), it is possible that not all the collagen fibers of the cornea and sclera are actually contributing to bear the loads. To the best of our knowledge, the fraction of corneoscleral shell fibers recruited and contributing to bear the load of IOP has not been reported. Our goal was to obtain regionally-resolved estimates of the fraction of corneoscleral collagen fibers recruited and in reserve. We developed a fiber-based microstructural constitutive model that could account for collagen fiber undulations or crimp via their tortuosity. We used experimentally-measured collagen fiber crimp tortuosity distributions in human eyes to derive region-specific nonlinear hyperelastic mechanical properties. We then built a three-dimensional axisymmetric model of the globe, assigning region-specific mechanical properties and regional anisotropy. The model was used to simulate the IOP-induced shell deformation. The model-predicted tissue stretch was then used to quantify collagen recruitment within each shell region. The calculations showed that, at low IOPs, collagen fibers in the posterior equator were recruited the fastest, such that at a physiologic IOP of 15 mmHg, over 90% of fibers were recruited, compared with only a third in the cornea and the peripapillary sclera. The differences in recruitment between regions, in turn, mean that at a physiologic IOP the posterior equator had a fiber reserve of only 10%, whereas the cornea and peripapillary sclera had two thirds. At an elevated IOP of 50 mmHg, collagen fibers in the limbus and the anterior/posterior equator were almost fully recruited, compared with 90% in the cornea and the posterior sclera, and 70% in the peripapillary sclera and the equator. That even at such an elevated IOP not all the fibers were recruited suggests that there are likely other conditions that challenge the corneoscleral tissues even more than IOP. The fraction of fibers recruited may have other potential implications. For example, fibers that are not bearing loads may be more susceptible to enzymatic digestion or remodeling. Similarly, it may be possible to control tissue stiffness through the fraction of recruited fibers without the need to add or remove collagen.
胶原蛋白是角膜和巩膜的主要承重成分。当这些组织被拉伸时,它们都会表现出一种称为胶原纤维募集的行为。在募集过程中,随着组织的拉伸,组成性胶原纤维会失去其自然的波纹,逐渐变直。募集的、笔直的纤维比非募集的、波浪形的纤维承受更大的机械载荷。因此,募集过程是角膜巩膜壳的公认的非线性宏观行为的基础。募集有一个有趣的含义:当募集不完全时,只有一部分胶原纤维实际上参与承受载荷,其余部分则“备用”。换句话说,在给定的眼内压(IOP)下,角膜和巩膜的胶原纤维并非全部实际参与承受载荷。据我们所知,募集并参与承受 IOP 载荷的角膜巩膜壳纤维的比例尚未报道。我们的目标是获得募集并参与承受 IOP 载荷的角膜巩膜胶原纤维的区域分辨率估计。我们开发了一种基于纤维的微观结构本构模型,该模型可以通过其扭曲来解释胶原纤维的起伏或卷曲。我们使用人眼中测量到的胶原纤维卷曲扭曲分布来推导出特定区域的非线性超弹性力学特性。然后,我们构建了一个三维轴对称的眼球模型,分配了特定区域的力学特性和区域各向异性。该模型用于模拟 IOP 诱导的壳变形。然后,使用模型预测的组织拉伸来量化每个壳区域内的胶原募集。计算结果表明,在低 IOP 下,后赤道处的胶原纤维募集最快,因此在生理 IOP 为 15mmHg 时,超过 90%的纤维被募集,而在角膜和视盘周围巩膜中仅募集三分之一。区域之间募集的差异意味着,在生理 IOP 下,后赤道的纤维储备仅为 10%,而角膜和视盘周围巩膜的纤维储备为三分之二。在升高的 IOP 为 50mmHg 时,角膜和巩膜的纤维几乎完全募集,而前/后赤道的纤维募集率为 90%,视盘周围巩膜和赤道的纤维募集率为 70%。即使在如此高的 IOP 下,并非所有纤维都被募集,这表明可能还有其他条件比 IOP 更能挑战角膜巩膜组织。募集的纤维比例可能还有其他潜在的影响。例如,未承受载荷的纤维可能更容易受到酶消化或重塑的影响。同样,可以通过募集的纤维比例来控制组织的刚度,而无需添加或去除胶原蛋白。