Biomechanics of Schlemm's canal endothelium and intraocular pressure reduction.

Biomechanics of Schlemm's canal endothelium and intraocular pressure reduction.
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DOI:
10.1016/j.preteyeres.2014.08.002
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发表时间:
2015-01
影响因子:
17.8
通讯作者:
Johnson, Mark
Johnson, Mark
中科院分区:
医学1区
文献类型:
--
作者:
Stamer, W. Daniel;Braakman, Sietse T.;Zhou, Enhua H.;Ethier, C. Ross;Fredberg, Jeffrey J.;Overby, Darryl R.;Johnson, Mark

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青光眼的高眼压是由于与年龄相关的流出道细胞功能障碍,导致对房水流出的抵抗力增加。两种类型的细胞,小梁网(TM)和Schlemm管(SC)内皮细胞,在常规流出道的管旁组织(JCT)区域相互作用,调节流出阻力。与衬里全身血管系统的内皮细胞不同,衬里SC内壁的内皮细胞支持从基底部到顶端方向的跨细胞压力梯度,从而将细胞推离其基底板。在SC细胞中产生的生物力学应变相当大,可能是内皮屏障功能、流出阻力和眼压的重要决定因素。本文综述了干细胞的生物力学特性如何影响青光眼的最新工作。干细胞是高度收缩的,这种收缩大大增加了细胞的硬度。青光眼中细胞硬度的增加可能会减少SC细胞所经历的压力,降低SC细胞形成孔洞的倾向,从而损害眼部房水的出口。此外,干细胞对其局部机械微环境的刚性很敏感,增加了自身细胞的刚性,并调节了相应的基因表达。值得注意的是,青光眼干细胞似乎对基质僵硬高度敏感。因此,有证据表明,靶向SC细胞的材料特性将对降低青光眼的眼压有治疗作用。
Ocular hypertension in glaucoma develops due to age-related cellular dysfunction in the conventional outflow tract, resulting in increased resistance to aqueous humor outflow. Two cell types, trabecular meshwork (TM) and Schlemm's canal (SC) endothelia, interact in the juxtacanalicular tissue (JCT) region of the conventional outflow tract to regulate outflow resistance. Unlike endothelial cells lining the systemic vasculature, endothelial cells lining the inner wall of SC support a transcellular pressure gradient in the basal to apical direction, thus acting to push the cells off their basal lamina. The resulting biomechanical strain in SC cells is quite large and is likely to be an important determinant of endothelial barrier function, outflow resistance and intraocular pressure. This review summarizes recent work demonstrating how biomechanical properties of SC cells impact glaucoma. SC cells are highly contractile, and such contraction greatly increases cell stiffness. Elevated cell stiffness in glaucoma may reduce the strain experienced by SC cells, decrease the propensity of SC cells to form pores, and thus impair the egress of aqueous humor from the eye. Furthermore, SC cells are sensitive to the stiffness of their local mechanical microenvironment, increasing their own cell stiffness and modulating gene expression in response. Significantly, glaucomatous SC cells appear to be hyper-responsive to substrate stiffness. Thus, evidence suggests that targeting the material properties of SC cells will have therapeutic benefits for lowering intraocular pressure in glaucoma.
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