Abstract
Purpose:
To investigate the effects of Y27632 on the hydrodynamic and morphological changes in laser-induced ocular hypertensive monkey eyes.
Methods:
Argon laser photocoagulation burns were made to the trabecular meshwork (TM) of cynomolgus monkey eyes to create chronic ocular hypertension(N=4). Normal untreated eyes served as a control(N=3). Enucleated eyes were perfused at pre-mortem intraocular pressure (by pneumatonometry) minus 7 mmHg to obtain a stable outflow facility (C). A two-color fluorescent tracer method was used to label aqueous outflow patterns before (green tracer, 0.5μm; 0.002%) and after Y27632 treatment (red tracer, 0.2μm; 0.002%). After removing remaining green tracer from the anterior chamber, eyes were perfused with 50μM Y27632. The anterior chamber contents were exchanged and perfused with red tracer. All eyes were perfused with a fixed volume of tracer and Y27632. Eyes were perfusion-fixed and C was continuously recorded. After global tracer distribution was imaged, the TM of all eyes was frontally sectioned for confocal microscopy. Total length(TL) and filtration length(FL) of both red and green tracer along the inner wall of Schlemm’s canal (SC) were measured for percent effective filtration length (PEFL=FL/TL). Student's t-test was used for statistical analysis. Results are Mean±SD.
Results:
The average IOP was 40.0±19.1 mmHg in laser-treated and 25.1±1.1mmHg in control eyes. The C was lower but not significantly in laser-treated compared to control eyes (0.21±0.19 vs. 0.52±0.23 μl/min/mmHg). After Y27632 treatment, C increased from baseline for both control (27.3±16.2 %) and laser-treated eyes (38.8±26.2%). By confocal microscopy, SC was open and a segmental distribution of both green and red tracer was seen in the TM of normal eyes while less tracer labeling was seen along SC in laser-treated eyes. PEFL for green tracer was significantly lower in laser-treated eyes compared to control eyes (10.1±5.3 % vs.42.2±12.5 %, p<0.01). PEFL for red tracer was significantly increased after Y27632 treatment in both laser-treated (16.3±7.4 %, p=0.05) and control (51.5±10.2 %, p=0.02) eyes.
Conclusions:
Y27632 increased C in both laser-induced ocular hypertensive and control eyes, which is associated with increased effective filtration area. The results suggest Y27632 increases C through increasing active flow area of the TM.
Keywords: 633 outflow: trabecular meshwork •
503 drug toxicity/drug effects •
596 microscopy: confocal/tunneling