The effect of intravitreal and topical prostaglandins on intraocular inflammation.
We investigated the effects of prostaglandins (PG) E2, PGD2, PGI2, and its metabolites 6-keto-PGE1 and 6-keto-PGF1 alpha, and U46619 (stable analogue of the PG endoperoxide, PGH2) administered either intravitreally or topically on intraocular pressure (IOP), pupil diameter, aqueous protein, and the entry of polymorphonuclear cells (PMNs) in the aqueous. PGE2, 6-keto-PGE1, U46619, and PGI2 increased IOP after either intravitreal or topical administration in a dose-dependent manner, 6-keto-PGE1 was the most potent in increasing IOP. U46619 and PGI2 increased IOP when administered intravitreally; however, these agents also increased IOP of the contralateral control eye. High doses of 6-keto-PGE1 and PGI2 but not 6-keto-PGF1 alpha or PGE2 increased the IOP of both experimental and contralateral eyes, suggesting that this effect may be due to the entry of these agents into the systemic or intraorbital circulation or to stimulation of neuronal pathways. Intravitreal administration of 6-keto-PGE1, PGE2, and PGI2 increased protein of the aqueous, with 6-keto-PGE1 significantly more potent than other PGs. Topically applied PGE2 and 6-keto-PGE1 also increased protein content of the aqueous at doses that elevated IOP. However, topical 6-keto-PGE1 alpha at doses that increased IOP did not increase protein content of the aqueous. In contrast, PGD2 increased the IOP in both eyes; however, it significantly increased aqueous protein content of the experimental eye, indicating that increase in protein content of the aqueous and increase in IOP are not necessarily associated. None of the PGs tested in this study had any effect on pupil diameter or PMN entry into the aqueous. Therefore the classic signs of intraocular inflammation, i.e., increase in IOP, increase in protein content of the aqueous, miosis, and PMN entry into aqueous, are not necessarily associated and sequential, and PGs do not induce all signs of inflammation.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000287:Administration, Topical; D000527:Alprostadil / Q000031:analogs & derivatives*; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000502:physiology; D011464:Epoprostenol / Q000008:administration & dosage / Q000494:pharmacology; D005123:Eye / Q000187:drug effects*; D005136:Eye Proteins / Q000502:physiology; D007249:Inflammation / Q000378:metabolism; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000502:physiology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011453:Prostaglandins / Q000008:administration & dosage / Q000494:pharmacology*; D011457:Prostaglandins D / Q000008:administration & dosage / Q000494:pharmacology; D011458:Prostaglandins E / Q000008:administration & dosage / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects; D011817:Rabbits; D014822:Vitreous Body
D005136:Eye Proteins; D011450:Prostaglandin Endoperoxides, Synthetic; D011453:Prostaglandins; D011457:Prostaglandins D; D011458:Prostaglandins E; C022950:6-ketoprostaglandin E1; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011464:Epoprostenol; D000527:Alprostadil