Effects of Y27632 on aqueous humor outflow facility with changes in hydrodynamic pattern and morphology in human eyes.
OBJECTIVE
To determine the effect of Y27632, a Rho-kinase inhibitor on aqueous outflow facility, flow pattern, and juxtacanalicular tissue (JCT)/trabecular meshwork (TM) morphology in human eyes.


METHODS
Sixteen enucleated human eyes were perfused with PBS plus glucose (GPBS) at 15 mm Hg to establish the baseline outflow facility. Six eyes were perfused for short-duration (30 minute) with either 50 μM Y27632 or GPBS (n = 3 per group). Ten eyes were perfused for long duration (3 hours) with either 50 μM Y27632 or GPBS (n = 5 per group). Outflow pattern was labeled using fluorescent microspheres, and effective filtration length (EFL) was measured. Morphologic changes and their relationship to EFL and facility were analyzed.


RESULTS
Outflow facility significantly increased after short-duration perfusion with Y27632 compared with its own baseline (P = 0.03), but did not reach statistical significance compared with its controls (P = 0.07). Outflow facility (P = 0.01) and EFL (P < 0.05) were significantly increased after long-duration perfusion with Y27632 compared with its controls. Increases in outflow facility and EFL demonstrated a positive correlation. Morphologically, the TM and JCT of high-tracer regions were more expanded compared with low-tracer regions. A significant increase in JCT thickness was found in the long-duration Y27632 group compared with its control group (10.0 vs. 8.0 μm, P < 0.01).


CONCLUSIONS
Y27632 increases outflow facility in human eyes. This increase correlates positively with an increase in EFL, which is associated with an increased expansion in the JCT. Our data suggest that EFL could serve as a novel parameter to correlate with outflow facility.
Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Chen-Yuan Charlie
CY
Yang
Ye
Y
Liu
Zhaozeng
Z
Lu
Ruiyi
R
Ren
Haiyan
H
Gong
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000577:Amides / Q000494:pharmacology*; D001082:Aqueous Humor / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008875:Middle Aged; D011725:Pyridines / Q000494:pharmacology*; D012044:Regression Analysis; D014129:Trabecular Meshwork / Q000187:drug effects / Q000648:ultrastructure; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
D000577:Amides; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases
Y27632; confocal and electron microscopy; effective filtration area; light; morphology; outflow facility; rho-kinase inhibitor; trabecular meshwork