Disturbed stress-mediated remodeling of the lens capsule after cataract surgery determines implanted accommodative intraocular lens efficacy

项目总结 白内障手术是老年人群中最常见的医疗程序，有近300万患者 每年仅在美国接受治疗。在这一过程中，白内障晶状体纤维通过一种 位于晶状体前部的称为连续圆形撕囊(CCC)的永久性孔 植入人工晶状体(IOL)。对此，残留晶状体上皮细胞 晶状体囊变得纤维化，导致晶状体囊膜变形和混浊，从而导致视力 对病人的骚扰。这种纤维化反应在调节性人工晶状体(AIOL)中尤其激进， 其试图恢复透镜将焦点从远物体改变到近物体的能力。虽然数量众多 人工晶状体的设计已经被提出，其疗效是有限的，因为纤维化反应使其丧失能力。 我们之前的工作强烈地表明，晶状体囊应力场的永久性破坏 在白内障手术过程中会导致纤维化反应和重塑。这一重塑过程最终会改变 人工晶状体的疗效包括纤维化反应和调节功能。尽管如此 关联，很少有模型被开发来评估晶状体囊-人工晶状体的相互作用，而且还没有模型 被认为是白内障手术后机械结构的改变。因此，这个项目的目标是开发第一个3- 手术后晶状体囊膜的三维有限元模型考虑应力调节的改变 白内障手术后的时间。该模型将用于实现两个目标。首先，我们将测试它是否能够 预测植入张力环的晶状体囊袋的力学和生物重塑(用于量化 白内障手术后晶状体囊纤维性收缩的程度)。第二，该模型将被用于 预测人工晶状体植入后随时间推移的疗效，作为CCC大小的函数。这两个目标将被比较 以报告经验数据，以验证模型的预测能力。这项工作有望提供 白内障手术后晶状体囊随时间变化的机械干扰的定量表征 以及对它如何驱动细胞介导的重塑过程的洞察。这对于预测疗效很重要。 植入人工晶状体和开发功能性人工晶状体，这被广泛认为是最后一个未被征服的 屈光手术的前沿。此外，该模型的结果将提供对机械驱动程序的深入了解 对纤维化细胞行为的研究将提高我们对包膜纤维化和植入的机制的理解 人工晶状体功能障碍。这些见解将为我们的实验工作提供信息并指导我们进一步了解 包膜纤维化的机械和生物驱动因素。这一理解也可以转化为阐明 一般来说，纤维化的过程被认为与全球近一半的死亡有关，以 更好地了解身体其他部位疾病的病因。

PROJECT SUMMARY Cataract surgery is the most common medical procedure in the aged population, with nearly 3 million patients treated annually in the U.S. alone. During this procedure, the cataractous lens fibers are removed through a permanent hole called a continuous circular capsulorhexis (CCC) placed in the anterior portion of the lens capsule and replaced with an artificial intraocular lens (IOL). In response, lens epithelial cells of the remnant lens capsule become fibrotic, causing distortion and opacification of the lens capsule that can lead to visual disturbances to the patient. This fibrotic response is particularly aggressive in accommodative IOLs (AIOLs), which attempt to restore the ability of the lens to change focus from distant to near objects. Although numerous AIOL designs have been proposed, their efficacy is limited as the fibrotic response renders them incapacitated. Our previous work has strongly suggested that the permanent disruption to the stress field of the lens capsule during cataract surgery drives the fibrotic response and remodeling. This remodeling process ultimately changes IOL efficacy both in terms of the fibrotic response and, when applicable, accommodative function. Despite these associations, few models have been developed to assess lens capsule-IOL interactions, and no model has considered altered mechanics after cataract surgery. Therefore, the goal of this project is to develop the first 3- D finite element model of the post-surgical lens capsule to consider altered stress-mediated adaptations over time after cataract surgery. The model will be used to accomplished two aims. First, we will test whether it can predict mechanical and biological remodeling of the lens capsule with implanted tension ring (used to quantify the degree of fibrotic contraction of the lens capsule after cataract surgery). Second, the model will be used to predict the efficacy of an AIOL over time after implantation, as a function of CCC size. Both aims will be compared to reported empirical data to validate the predictive capability of the model. This work is expected to provide quantitative characterization of the mechanical disturbance to the lens capsule over time after cataract surgery and insights into how it drives the cell-mediated remodeling process. This is important for predicting the efficacy of an implanted IOL and developing a functional AIOL, which is widely considered to be the last unconquered frontier in refractive eye surgery. In addition, the results of this model will provide insights into mechanical drivers of fibrotic cellular behaviors that will improve our understanding of capsular fibrosis and mechanisms of implanted intraocular lens dysfunction. These insights will inform and direct our experimental efforts to further understand mechanical and biological drivers of capsular fibrosis. This understanding can also be translated to shed light on the process of fibrosis, in general, which is thought to be associated with nearly half of all deaths worldwide, to better understand the etiology of diseases in other parts of the body.