Multi-scale analysis of segmental outflow patterns in human trabecular meshwork with changing intraocular pressure.
OBJECTIVE
Aqueous humor filtration in the trabecular meshwork is believed to be non-uniform or "segmental" such that only a fraction of trabecular meshwork is filtration-active at any given instant. The goal was to quantify the filtration-active fraction of human trabecular meshwork and to determine how filtration patterns change with outflow facility and intraocular pressure (IOP).


METHODS
Six pair of enucleated human eyes were perfused with fluorescent tracer microspheres (0.2 μm) at 7 or 30 mmHg. Tracer patterns were imaged over the "macro-scale" (0.1-10 mm) using epifluorescence microscopy and "micro-scale" (10-100 μm) using confocal microscopy. Quantitative image analysis was used to measure the tracer-labeled fraction and to examine co-localization with trabecular pigmentation and the location of collector channel ostia.


RESULTS
Tracer distribution was segmental over both macro-scale and micro-scale dimensions. No more than approximately one-third of the trabecular meshwork appeared to be filtration-active on the macro scale (29%±5%; mean±SD) and micro scale (21%±6%). There was weak co-localization between macro-scale tracer intensity and pigmentation (r=0.17, P=0.017), and collector channel ostia tended to coincide with regions of high macro-scale tracer intensity. Tracer patterns were relatively insensitive to changing IOP over hour-long time scales and did not correlate with outflow facility.


CONCLUSIONS
Filtration patterns in human trabecular meshwork appear segmental over both macro-scale and micro-scale dimensions, with only approximately one-third of the trabecular meshwork actively contributing to outflow. Segmental outflow may limit the efficacy of outflow drugs by preventing delivery to non-filtering trabecular regions that may contribute the most to outflow obstruction in glaucoma.
1 Department of Bioengineering, Imperial College London , London, United Kingdom .
Jason Y H
JY
Chang
Steven J
SJ
Folz
Susuana N
SN
Laryea
Darryl R
DR
Overby
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001082:Aqueous Humor / Q000502:physiology*; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology*; D018613:Microscopy, Confocal / Q000379:methods; D008856:Microscopy, Fluorescence / Q000379:methods; D008875:Middle Aged; D014129:Trabecular Meshwork / Q000502:physiology*