Abstract
Abstract: :
Purpose:To determine the effects of 8-iso PGE2 on trabecular outflow facility (Ctrab) and uveoscleral outflow (Fu) in cynomolgus monkeys. Methods:Monkeys (n=17) were treated topically twice a day with 25ug 8-iso PGE2 to one eye, vehicle to the opposite eye. Intraocular pressure (IOP) response was determined on the 4th day. Treatment was continued until the experimental day (days 5-15). Total aqueous humor formation (AHF) and flow of aqueous humor to the general blood circulation (FTB) were determined in both eyes beginning 2 hr after that day's treatment. AHF was measured by dilution of radio-iodinated monkey albumin (I-MSA) perfused through the anterior chamber, and FTB by accumulation of I-MSA in the general circulation. Fu was the difference between AHF and FTB. Ctrab was determined by exchanging the anterior chamber with I-MSA, then measuring FTB while IOP was alternated between two pressures with flow from an elevated reservoir containing the corresponding I-MSA. Ctot was also determined by two-level constant pressure perfusion at the conclusion of the isotope measurements. Results:Following 8-iso PGE2, IOP decreased by 2-3 mmHg in most groups of animals by the 4th day of treatment. On days 5-15, AHF (PG=1.22±0.09; cont=1.23±0.09 µl/min, n=10), Ctot (PG=0.30±0.04; cont=0.28±0.03 µl/min/mmHg, n=11), and Ctrab (PG=0.35±0.05; cont=0.45±0.07 µl/min/mmHg, n=11) were unchanged. FTB decreased (PG=0.33±0.12; cont=0.77±0.12 µl/min, n=10, p=0.011), while Fu increased (PG=0.89±0.15; cont=0.46±0.11 µl/min, n=10) as did the ratio Fu/AHF (PG=0.71±0.10; cont=0.36±0.09, n=10, p=0.043). Conclusion:8-iso PGE2 appears to lower IOP by increasing Fu, but not as dramatically as previously reported for PGF2α-ie and analogues. Previously reported increases in Ctot measured by perfusion and/or tonography after 8-iso PGE2 but not latanoprost appear not to be due to an effect on Ctrab as measured by the presently employed technique. Further studies are needed to determine if as yet unknown mechanisms may be involved in the IOP response to 8-iso PGE2.
Keywords: 392 eicosanoids • 502 outflow: ciliary muscle • 503 outflow: trabecular meshwork