The changing paradigm of outflow resistance generation: towards synergistic models of the JCT and inner wall endothelium.
The changing paradigm of outflow resistance generation: towards synergistic models of the JCT and inner wall endothelium.
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流出阻力产生的不断变化的范式：朝向JCT和内壁内皮的协同模型。
DOI：
10.1016/j.exer.2008.11.033
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发表时间：
2009-04
影响因子：
3.4
通讯作者：
Johnson, Mark
中科院分区：
文献类型：
--
作者：
Overby, Darryl R.;Stamer, W. Daniel;Johnson, Mark
关键词：
房水流出阻力是决定眼内压的主要因素，而房水流出阻力增加是青光眼相关眼压升高的基础。实验证据表明，大部分流出阻力产生于Schlemm管内壁内皮、基底膜和管旁结缔组织(JCT)附近。然而，试图找出这些组织中的每一个对总流出阻力的贡献都没有成功。传统的流出阻力理论认为，流出通道中各组织层(即内壁内皮细胞、基底膜和JCT)的阻力串联相加，从而导致总流出阻力的产生。然而，这种观点导致了一个悖论，即流出通道中所有组织的表观阻力远远低于测量的总阻力。为了解决这一悖论，我们探索了流出阻力产生的协同模型，其中不同组织层之间的流体动力相互作用导致总阻力大于单个组织阻力的总和。我们仔细研究了“漏斗”假说，它已经成为一个领先的协同模型，我们回顾了漏斗的基础，漏斗的机械和生物学要求，以及支持这一假说的证据。我们还建议对漏斗模型进行改进，并描述漏斗如何与小梁网内观察到的房水流出模式的节段性变异性有关。横跨JCT和内壁内皮的压力梯度会产生机械载荷，影响这些组织的形态。由于组织形态可能反过来影响流出阻力，因此在流出流体力学与内壁和JCT的力学行为之间存在双向耦合或“流固相互作用”的可能性。此外，内壁和JCT之间的粘连和系绳必须在物理上能够支撑这样的载荷。我们检查了这些粘合剂的结构和机械强度，并提供了证据，证明这些粘合剂和系绳不能支持大部分流出阻力产生的全部载荷，除非JCT内产生相当大一部分流出阻力，这与漏斗模型一致。这表明内壁和JCT之间的这些附着物对流出阻力的调节具有重要的生理意义，这方面的研究还有待于进一步的研究。
Aqueous humor outflow resistance is the primary determinant of intraocular pressure (IOP), and increased outflow resistance is the basis for elevated IOP associated with glaucoma. Experimental evidence suggests that the bulk of outflow resistance is generated in the vicinity of the inner wall endothelium of Schlemm’s canal, its basement membrane and the juxtacanalicular connective tissue (JCT). However, attempts to sort out the contribution of each of these tissues to total outflow resistance have not been successful. Conventional understanding of outflow resistance assumes that the resistance of each tissue strata (i.e., the inner wall endothelium, its basement membrane and JCT) in the outflow pathway adds in series to contribute to total outflow resistance generation. However, this perspective leads to a paradox where the apparent resistances of all tissues in the outflow pathway are much lower than the measured total resistance. To resolve this paradox, we explore synergistic models of outflow resistance generation where hydrodynamic interactions between different tissue strata lead to a total resistance that is greater than the sum of the individual tissue resistances. We closely examine the “funneling” hypothesis that has emerged as a leading synergistic model, and we review the basis of funneling, mechanical and biological requirements for funneling and evidence in support of this hypothesis. We also propose refinements to the funneling model and describe how funneling may relate to segmental variability of aqueous humor outflow patterns observed within the trabecular meshwork. Pressure gradients across the JCT and inner wall endothelium will generate mechanical loads that influence the morphology of these tissues. Because tissue morphology may in turn affect outflow resistance, there exists the potential for a two-way coupling or a “fluid-solid interaction” between outflow hydrodynamics and the mechanical behavior of the inner wall and JCT. Furthermore, the adhesions and tethers between the inner wall and JCT must be physically capable of supporting such loads. We examine the structure and mechanical strength of these adhesions, and provide evidence that these adhesions and tethers are unable to support the full load imposed by the bulk of outflow resistance generation unless a substantial fraction of outflow resistance is generated within the JCT, consistent with the funneling model. This indicates that these attachments between the inner wall and JCT have considerable physiological importance for outflow resistance regulation, and further study is greatly needed in this area.
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影响因子：
64.5
作者：
Choquet, D;Felsenfeld, DP;Sheetz, MP
通讯作者：
Sheetz, MP
DOI：
10.1111/j.1748-1716.1954.tb01092.x
发表时间：
1954-01-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
BARANY, EH;SCOTCHBROOK, S
通讯作者：
SCOTCHBROOK, S
DOI：
10.1098/rspb.1988.0038
发表时间：
1988-06-22
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DEMBO, M;TORNEY, DC;HAMMER, D
通讯作者：
HAMMER, D
DOI：
10.1083/jcb.200403043
发表时间：
2004-12-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chu YS;Thomas WA;Eder O;Pincet F;Perez E;Thiery JP;Dufour S
通讯作者：
Dufour S
DOI：
10.1111/j.1748-1716.1955.tb01208.x
发表时间：
1955-01-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
BARANY, EH;WOODIN, AM
通讯作者：
WOODIN, AM