Effects of exogenous prostaglandins on aqueous humor dynamics and blood-aqueous barrier function

• Published in: Survey of ophthalmology Vol. 41; pp. S69 - S75
• Main Authors: Toris, Carol B., Camras, Carl B., Yablonski, Michael E., Brubaker, Richard F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.1997
• Subjects: Animals; Aqueous Humor - drug effects; Aqueous Humor - metabolism; aqueous humor dynamics; Blood-Aqueous Barrier - drug effects; Blood-Aqueous Barrier - physiology; Capillary Permeability - drug effects; cat; Cats; Haplorhini; human; Humans; Intraocular Pressure - drug effects; latanoprost; monkey; outflow facility; prostaglandin; Prostaglandins - pharmacology; Rabbits; uveoscleral outflow; latanoprost; outflow facility; monkey; prostaglandin; uveoscleral outflow; cat; aqueous humor dynamics; human
• ISSN: 0039-6257; 1879-3304
• DOI: 10.1016/S0039-6257(97)80010-0

Topical prostaglandins (PGs) are very effective at reducing intraocular pressure (IOP) in a variety of animals and in humans with relatively few side effects. The mechanisms of action of several PGs, their prodrugs and analogues have been studied in rabbits, cats, monkeys and humans. PGF 2α and its analogues evaluated in monkeys include PGF 2α-tromethamine salt, PGF 2α-isopropylester (-IE), S-1033, PhXA34, PhDH100A and latanoprost (PhXA41). Aqueous flow and outflow facility are either increased or remain unchanged by these agents. PGF 2α-IE, PHXA34, PhDH100A and latanoprost increase uveoscleral outflow, accounting for most of the IOP reduction. PGA 2 in cats increases aqueous flow and outflow facility, but it reduces IOP primarily by stimulating uveoscleral outflow. The PGD 2 analogue BW245C is unique in that it is the only PG that decreases aqueous flow. Mechanistic studies in humans have been performed with PGF 2α-IE, unoprostone, PhXA34 and latanoprost. In two clinical studies with latanoprost, a significant increase in uveoscleral outflow was found which, as in animals, accounts for most of the IOP reduction. A slight but inconsistent increase in outflow facility may also be involved, The doses tested had minimal effects on the permeability of the blood-aqueous barrier (BAB). In vitro studies of human tissue have been conducted to elucidate the PG effect on outflow facility and uveoscleral outflow. Studies of isolated human anterior segment preparations show that PGE 2 increases outflow facility whereas PGF 2α, has no measurable effect on this parameter. Studies of human ciliary muscle cells in tissue culture indicate that PGs may directly modulate extracellular matrix metabolism, which may be related to the increased uveoscleral drainage. This review summarizes in vitro and in vivo studies of the effects of PGs on aqueous humor dynamics and BAB integrity in humans, cats and monkeys.