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Abstract：
All aqueous humor draining through the conventional outflow pathway must cross the endothelium of Schlemm\'s canal (SC), likely by passing through micron-sized transendothelial pores. SC pores are non-uniformly distributed along the inner wall endothelium, but it is unclear how the distribution of pores relates to the non-uniform or segmental distribution of aqueous humor outflow through the trabecular meshwork. It is hypothesized that regions in the juxtacanalicular tissue (JCT) with higher local outflow should coincide with regions of greater inner wall pore density compared to JCT regions with lower outflow. Three pairs of non-glaucomatous human donor eyes were perfused at 8 mmHg with fluorescent tracer nanospheres to decorate local patterns of outflow segmentation through the JCT. The inner wall was stained for CD31 and/or vimentin and imaged en face using confocal and scanning electron microscopy (SEM). Confocal and SEM images were spatially registered to examine the spatial relationship between inner wall pore density and tracer intensity in the underlying JCT. For each eye, tracer intensity, pore density (n) and pore diameter (D) (for both transcellular \"I\" and paracellular \"B\" pores) were measured in 4-7 regions of interest (ROIs; 50 × 150 μm each). Analysis of covariance was used to examine the relationship between tracer intensity and pore density, as well as the relationship between tracer intensity and three pore metrics (nD, nD(2) and nD(3)) that represent the local hydraulic conductivity of the outflow pathway as predicted by various hydrodynamic models. Tracer intensity in the JCT correlated positively with local pore density when considering total pores (p = 0.044) and paracellular B pores on their own (p = 0.016), but not transcellular I-pores on their own (p = 0.54). Local hydraulic conductivity as predicted by the three hydrodynamic models all showed a significant positive correlation with tracer intensity when considering total pores and B-pores (p < 0.0015 and p < 10(-4)) but not I-pores (p > 0.38). These data suggest that aqueous humor passes through micron-sized pores in the inner wall endothelium of SC. Paracellular B-pores appear to have a dominant contribution towards transendothelial filtration across the inner wall relative to transcellular I-pores. Impaired pore formation, as previously described in glaucomatous SC cells, may thereby contribute to greater outflow heterogeneity, outflow obstruction, and IOP elevation in glaucoma.
摘要：
所有通过常规流出途径引流的房水必须穿过Schlemm管（SC）的内皮，可能通过微米大小的跨内皮孔。SC孔沿内壁内皮不均匀分布，但尚不清楚毛孔的分布与房水通过小梁网流出的不均匀或分段分布有何关系。假设与流出量较低的JCT区域相比，局部流出量较高的结膜组织（JCT）中的区域应与内壁孔密度较大的区域重合。在8mmHg下用荧光示踪剂纳米球灌注三对非青光眼人类供体眼睛，以通过JCT装饰流出分割的局部模式。对内壁进行CD31和/或波形蛋白染色,并使用共聚焦和扫描电子显微镜(SEM)成像。在空间上配准共聚焦和SEM图像，以检查下层JCT中内壁孔密度与示踪剂强度之间的空间关系。对于每一只眼睛，示踪强度,在4-7个感兴趣的区域（ROI；每个50×150μm）中测量了孔密度（n）和孔径（D）（跨细胞“I”和细胞旁“B”孔）。协方差分析用于检查示踪剂强度与孔隙密度之间的关系，以及示踪剂强度与三个孔隙指标(nD，nD（2）和nD（3））表示各种流体动力学模型预测的流出路径的局部水力传导率。当考虑总孔（p=0.044）和细胞旁B孔（p=0.016）时，JCT中的示踪剂强度与局部孔密度呈正相关。但不是跨细胞的I孔本身（p=0.54）。当考虑总孔和B孔（p<0.0015和p<10（-4））而不是I孔（p>0.38）时，由三个流体动力学模型预测的局部水力传导率均显示出与示踪剂强度的显着正相关。这些数据表明房水通过SC内壁内皮中的微米大小的孔。相对于跨细胞I孔，细胞旁B孔似乎对穿过内壁的跨内皮过滤具有主要贡献。孔隙形成受损,如先前在青光眼SC细胞中所述，因此可能会导致更大的流出异质性，流出道阻塞,青光眼患者眼压升高。
