The primary biomechanical driver of pathological glaucomatous cupping remains unknown. Finite element modelling indicates that stress and strain play key roles. Primarily a review article we utilise known biomechanical data and currently unpublished results from our lab to propose a 3 stage, tissue stiffness-based model to explain glaucomatous cupping occurring at variable levels of translaminar pressure (TLP). In stage 1, a short-term increase in TLP gradient induces a transient increase in LC strain. Beyond a critical level of strain, the tissue stiffness rises steeply provoking cellular responses via integrin mediated mechanotransduction. This early mechanoprotective cellular contraction reduces strain which reduces tissue stiffness by return of the posteriorly deflected LC to baseline. In stage 2 a prolonged period of TLP increase elicits extracellular matrix (ECM) production leading to fibrosis, increasing baseline tissue stiffness and strain, and diminishing the contractile ability/ ability to return to the baseline LC position. This is supported by our 3D collagen contraction assays which show significantly reduced capacity to contract in glaucoma compared to normal LC cells. Secondly, 15% cyclic strain in LC cells over 24 hours elicits a typical increase in ECM profibrotic genes in normal LC cells, but a highly blunted response in glaucoma LC cells. Stage 3 is characterised by persistent fibrosis causing further stiffening and inducing a feed-forward ECM production cycle. Repeated cycles of increased strain and stiffness with profibrotic ECM deposition, prevent optic nerve head (ONH) recoil from the new deflected position. This incremental maladaptive modelling leads to pathological ONH cupping.

中文翻译：

---

薄层筛板的组织僵硬和纤维化是病理性青光眼拔罐的基本生物力学驱动力。

病理性青光眼拔罐的主要生物力学驱动因素仍然未知。有限元建模表明应力和应变起着关键作用。首先是一篇综述文章，我们利用已知的生物力学数据和我们实验室目前未发表的结果提出了一个基于组织刚度的三阶段模型，用于解释在不同水平的跨层压力（TLP）下发生的青光眼拔罐。在阶段1中，TLP梯度的短期增加会引起LC应变的瞬时增加。超过临界水平的应变，组织刚度急剧上升，通过整联蛋白介导的机械转导引起细胞反应。这种早期的机械保护性细胞收缩减少了应变，该应变通过使后偏转的LC返回基线而降低了组织的刚度。在阶段2中，TLP延长会引起细胞外基质（ECM）产生，从而导致纤维化，基线组织僵硬和应变增加，以及收缩能力/回到基线LC位置的能力下降。我们的3D胶原蛋白收缩测定法支持了这一点，与正常的LC细胞相比，该法显示了青光眼的收缩能力明显降低。其次，在24小时内LC细胞中15％的循环应变会引起正常LC细胞中ECM纤维化基因的典型增加，但在青光眼LC细胞中则反应迟钝。第三阶段的特征是持续性纤维化，引起进一步的僵硬并引发前馈ECM生产周期。纤维化ECM沉积导致应变和刚度增加的反复循环，可防止视神经头（ONH）从新的偏转位置后坐。