Alireza Karimi , Mini Aga , Ansel Stanik , Tia Harbaugh , Elise Coffey , Elizabeth White , Mary J. Kelley , Ted S. Acott
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引用次数: 0
Abstract
Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide, with an estimated 112 million people projected to be affected by 2040. The primary risk factor for POAG is elevated intraocular pressure (IOP), which is primarily driven by increased resistance to aqueous humor outflow through the conventional outflow pathway. Despite its prevalence, the precise biomechanical mechanisms underlying this resistance remain unclear. In this study, we utilized 3D in situ traction force microscopy to investigate the effects of the rho kinase (ROCK) inhibitor Y-27632 and the YAP/TAZ inhibitor Verteporfin treatments on the trabecular meshwork (TM) and juxtacanalicular tissue (JCT) cellular contractility and their extracellular matrix (ECM) reorganization in both normal and glaucomatous human donor eyes. Our analysis revealed dysregulated traction forces within glaucomatous tissues, leading to significant ECM reorganization that may contribute to disrupting the homeostasis of the aqueous outflow pathway. Treatments appear to help restore normal ECM structure by adjusting cellular forces. The effect on contractile forces differed between genders, suggesting the significance of gender in treatment response. Our results suggest that targeting these biomechanical pathways may offer new therapeutic strategies to reduce outflow resistance, laying the groundwork for future therapies aimed at preserving vision by restoring ECM biomechanics and improving outflow.
期刊介绍:
Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed.
Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.