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The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications
Progress in Retinal and Eye Research ( IF 17.8 ) Pub Date : 2017-03-12 , DOI: 10.1016/j.preteyeres.2017.03.001
Hongli Yang , Juan Reynaud , Howard Lockwood , Galen Williams , Christy Hardin , Luke Reyes , Cheri Stowell , Stuart K. Gardiner , Claude F. Burgoyne

In a series of previous publications we have proposed a framework for conceptualizing the optic nerve head (ONH) as a biomechanical structure. That framework proposes important roles for intraocular pressure (IOP), IOP-related stress and strain, cerebrospinal fluid pressure (CSFp), systemic and ocular determinants of blood flow, inflammation, auto-immunity, genetics, and other non-IOP related risk factors in the physiology of ONH aging and the pathophysiology of glaucomatous damage to the ONH. The present report summarizes 20 years of technique development and study results pertinent to the characterization of ONH connective tissue deformation and remodeling in the unilateral monkey experimental glaucoma (EG) model. In it we propose that the defining pathophysiology of a glaucomatous optic neuropathy involves deformation, remodeling, and mechanical failure of the ONH connective tissues. We view this as an active process, driven by astrocyte, microglial, fibroblast and oligodendrocyte mechanobiology. These cells, and the connective tissue phenomena they propagate, have primary and secondary effects on retinal ganglion cell (RGC) axon, laminar beam and retrolaminar capillary homeostasis that may initially be “protective” but eventually lead to RGC axonal injury, repair and/or cell death. The primary goal of this report is to summarize our 3D histomorphometric and optical coherence tomography (OCT)-based evidence for the early onset and progression of ONH connective tissue deformation and remodeling in monkey EG. A second goal is to explain the importance of including ONH connective tissue processes in characterizing the phenotype of a glaucomatous optic neuropathy in all species. A third goal is to summarize our current efforts to move from ONH morphology to the cell biology of connective tissue remodeling and axonal insult early in the disease. A final goal is to facilitate the translation of our findings and ideas into neuroprotective interventions that target these ONH phenomena for therapeutic effect.



中文翻译:

猴眼青光眼拔罐的结缔组织表型-临床及研究意义

在一系列先前的出版物中,我们已经提出了将视神经头(ONH)概念化为生物力学结构的框架。该框架为眼内压(IOP),与IOP相关的压力和劳损,脑脊髓液压力(CSFp),血流的系统和眼部决定因素,炎症,自身免疫,遗传学和其他与非IOP相关的危险因素提出了重要角色在ONH衰老的生理和青光眼损害ONH的病理生理中。本报告总结了20年的技术发展和与ONH结缔组织变形和重塑在单侧猴实验性青光眼(EG)模型中表征有关的研究结果。在这篇文章中,我们提出定义青光眼性视神经病变的病理生理学涉及变形,重塑,和ONH结缔组织的机械故障。我们认为这是一个活跃的过程,由星形胶质细胞,小胶质细胞,成纤维细胞和少突胶质细胞力学生物学驱动。这些细胞及其传播的结缔组织现象对视网膜神经节细胞(RGC)轴突,层流束和层后毛细血管稳态具有主要和次要作用,这些作用最初可能是“保护性的”,但最终会导致RGC轴突损伤,修复和/或细胞死亡。本报告的主要目的是总结基于3D组织形态计量学和光学相干断层扫描(OCT)的证据,以证明猴子EG中ONH结缔组织变形和重塑的早期发作和进展。第二个目标是解释在所有物种中表征青光眼性视神经病变的表型时,包括ONH结缔组织过程的重要性。第三个目标是总结我们目前从ONH形态向结缔组织重塑和疾病早期轴突损伤的细胞生物学转变的努力。最终目标是促进将我们的发现和想法转化为针对这些ONH现象的神经保护性干预措施,以达到治疗效果。

更新日期:2017-03-12
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