Multi-scale analysis of segmental outflow patterns in human trabecular meshwork with changing intraocular pressure

Area of Science:

• Ophthalmology
• Fluid Dynamics
• Cell Biology

Background:

• Aqueous humor outflow is crucial for maintaining intraocular pressure (IOP).
• Trabecular meshwork (TM) filtration is hypothesized to be non-uniform, or segmental.
• Understanding filtration patterns is key to addressing glaucoma pathophysiology.

Purpose of the Study:

• Quantify the filtration-active fraction of human trabecular meshwork.
• Determine how filtration patterns correlate with outflow facility and IOP.
• Investigate the spatial distribution of filtration activity.

Main Methods:

• Perfused enucleated human eyes with fluorescent tracer microspheres.
• Imaged tracer distribution at macro- and micro-scales using epifluorescence and confocal microscopy.
• Analyzed tracer patterns, co-localization with pigmentation, and collector channel ostia.

Main Results:

• Filtration was confirmed as segmental across both macro- and micro-scales.
• Approximately one-third of the TM (29% macro, 21% micro) was filtration-active.
• Tracer patterns were largely insensitive to IOP changes and did not correlate with outflow facility.

Conclusions:

• Human TM filtration is segmental, with limited active regions contributing to outflow.
• Segmental outflow may reduce the efficacy of IOP-lowering medications.
• Targeting non-filtering TM regions could be a strategy for glaucoma treatment.