Interendothelial junctions in normal human Schlemm's canal respond to changes in pressure

Area of Science:

• Ocular Physiology
• Cell Biology
• Glaucoma Research

Background:

• Schlemm's canal (SC) is crucial for aqueous humor outflow in the eye.
• The endothelial cell junctions of SC regulate the paracellular pathway.
• Understanding SC junction dynamics is vital for glaucoma pathogenesis.

Purpose of the Study:

• To investigate structural and complexity changes in SC endothelial cell junctions.
• To assess the impact of varying perfusion pressures on SC junction morphology in normal human eyes.

Main Methods:

• Normal human eyes were perfusion-fixed at different pressures (0, 15, 45 mm Hg).
• Ultrastructural examination of SC intercellular junctions using serial sections and freeze-fracture replicas.
• Morphometric analysis of junctional strand number and endothelial cell overlap length.

Main Results:

• Increased perfusion pressure led to less complex tight junctions in SC endothelial cells.
• A statistically significant decrease in junctional complexity (3+ strands) was observed with rising pressure (24.17% at 0 mm Hg vs. 8.59% at 45 mm Hg).
• Endothelial cell overlap and paracellular pathway length were reduced under perfusion fixation compared to immersion fixation.

Conclusions:

• SC endothelial cell overlap decreases significantly under physiological flow conditions.
• Tight junction complexity in the inner wall of SC diminishes as pressure increases.
• The paracellular pathway into SC is pressure-sensitive within physiologically relevant ranges.