Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America.
Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.
Sci Rep. 2018 Apr 3;8(1):5468. doi: 10.1038/s41598-018-23861-x.
Pigment dispersion can lead to pigmentary glaucoma, a poorly understood condition of younger myopic eyes with fluctuating high intraocular pressure. It has been difficult to investigate its pathogenesis without a model similar to human eyes in size and behavior. Here we present a porcine ex vivo model that recreates several features of pigmentary glaucoma, including intraocular hypertension, accumulation of pigment in the trabecular meshwork, and declining phagocytosis. We found that trabecular meshwork cells regulate outflow, form actin stress fibers, and have a decreased phagocytic activity. Gene expression microarrays and a pathway analysis of TM monolayers as well as ex vivo anterior segment perfusion cultures indicated that RhoA plays a central role in regulating the cytoskeleton, motility, and phagocytosis in the trabecular meshwork, providing new insights and targets to investigate in pigmentary glaucoma.
色素播散可导致色素性青光眼,这是一种未被充分了解的疾病,好发于年轻近视眼,其眼压波动较高。由于缺乏与人眼大小和行为相似的模型,因此很难研究其发病机制。在这里,我们提出了一个猪眼离体模型,该模型再现了色素性青光眼的几个特征,包括眼内高压、小梁网中色素的积累以及吞噬作用的下降。我们发现小梁网细胞调节房水流出、形成肌动蛋白应力纤维,并具有降低的吞噬活性。TM 单层的基因表达微阵列和通路分析以及离体前段灌注培养表明,RhoA 在调节小梁网的细胞骨架、运动和吞噬作用中发挥着核心作用,为研究色素性青光眼提供了新的见解和靶点。