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C Ethier, Sietse Braakman, Arthur Read, Darren Chan, Darryl Overby; Schlemm's Canal (SC) Inner Wall Pores Correlate with Segmental Outflow in Human Eyes. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3538.
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© ARVO (1962-2015); The Authors (2016-present)
Non-uniform drainage of aqueous humor (AH) through the trabecular meshwork (TM) likely influences outflow resistance, and SC inner wall (IW) pore density may influence local AH flow. Here we test whether regions of segmental outflow coincide with high IW pore density.
This study extends data from ARVO 2012. We labeled TM outflow patterns by perfusing 2 pairs of normal human enucleated eyes at 8 mmHg/37 °C with mock AH containing fluorescent microspheres. All eyes were fixed by immersion. IW/TM in outflow tissue wedges was examined by en face confocal microscopy and 4-7 150x50µm regions-of-interest (ROIs) with either high or low fluorescent tracer intensity were identified per wedge. Average tracer fluorescence intensity integrated over the JCT region was measured in each ROI. IW pore density (n) and diameters (D) were then measured in the same ROIs by scanning electron microscopy, and 5 IW pore metrics were computed in each ROI: Pk = nDk, for k = 0…4. Note P0 = pore density; P1 = nD-product, indicating strength of the funneling effect; P2, P3 and P4 are proportional to IW porosity, local fluid conductance from Sampson’s law and from Poiseuille’s law, respectively. Data were analyzed by ANCOVA with Bonferroni correction, as required.
All eyes had normal facility. Unlike pressure-fixed eyes, these immersion-fixed eyes had more paracellular [B] vs intracellular [I] pores (54% B pores). Tracer intensity correlated with total pore density (p=0.02). For I pores, Pk did not depend on tracer intensity for any k = 0…4, indicating that I pores did not co-localize with regions of high flow. However, for B pores, Pk was correlated with tracer intensity for all k=0…4, with p < 0.004 for all pore metrics.
B, but not I, pores co-localize with regions of high tracer representing segmental outflow, supporting the hypothesis that B pores are involved in fluid transport across the IW of SC. The very strong correlation between inner wall B pore metrics and tracer intensity is consistent with local outflow patterns being controlled by an interaction between flow through the JCT and across the IW. Further, our data are consistent with B pores being the “normal” AH route across the IW at lower pressures, with I pores providing a secondary route at higher pressures.
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