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S.R. Hofmann, H. Gong, Z. Lu, S.A. Kasper, P. Scott, D.R. Overby; Increasing IOP Reduces the Effective Filtration Area Through the JCT and Inner Wall in Bovine Eyes . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1860.
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Recent studies have shown that aqueous humor outflow is segmental rather than uniform, such that only a fraction of the total area of juxtacanalicular connective tissue (JCT) and inner wall is involved in aqueous humor filtration at any given instant. This area is termed the effective filtration area. To understand the functional significance of effective filtration area in aqueous humor outflow, we examined the quantitative relationship between effective filtration area and IOP in bovine eyes.
Bovine eyes were perfused at constant IOP (7, 15, 30 or 45 mmHg; n=21) with Dulbecco’s PBS and 5.5 mM glucose (DBG) while continually recording outflow facility. After 30 min, anterior chamber contents were exchanged with DBG containing red fluorescent microspheres (0.5 µm, 0.002% v/v), followed by 0.5 mL of tracer perfusion. The anterior chamber was then exchanged and perfusion fixed with Karnovsky’s fixative. Histologic sections were cut tangentially to the limbus in all four quadrants, counter–stained, and examined by confocal microscopy to visualize tracer labeling patterns in the trabecular meshwork, JCT and inner wall. Image analysis software was used to measure the total length of inner wall (TL) and the apparent length (L) of inner wall exhibiting tracer labeling in each image (n=8 to 19 images per eye). The effective filtration length (i.e., the 1–dimensional equivalent to effective filtration area observed on a micrograph) was calculated as L/TL for each image and averaged over all images per eye.
Outflow facility decreased with increasing IOP between 7 and 45 mmHg (1.65±0.25 vs 0.79±0.07 µL/min/mmHg; mean±SEM; p < 0.034). With increasing IOP, tracer labeling in the JCT and along the inner wall transitioned from a more uniform to a more confined pattern, tending to concentrate near collector channel ostia. Effective filtration length decreased from 0.57±0.04 at 7 mmHg to 0.27±0.05, 0.41±0.04, and 0.26±0.09 at 15, 30 and 45 mmHg, respectively (p<0.036, relative to 7 mmHg).
Increasing IOP leads to a significant decrease in effective filtration length that coincides with a decrease in outflow facility. These data suggest a potential mechanism where outflow facility is controlled by the effective filtration area and the segmentation of aqueous humor outflow that constrict outflow through the resistive tissues of the inner wall and JCT. If confirmed, this hypothetical mechanism would significantly improve our hydrodynamic understanding of aqueous humor outflow resistance.
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