Stimulation of cyclic adenosine monophosphate accumulation causes breakdown of the blood-retinal barrier.
Pigmented rabbits were given an intravitreous injection of 0.1 ml of various concentrations of test drug, and vitreous fluorophotometry was done 6 and 24 hr after injection. Dibutyryl cyclic adenosine monophosphate (AMP) and 8-bromo-cyclic AMP caused reversible intravitreous fluorescein leakage only at relatively high concentrations. Adrenergic agents that are effective stimulators of adenylate cyclase (epinephrine, isoproterenol, and norepinephrine) caused transient intravitreous fluorescein leakage (2.3-3.1-fold above baseline) that was significantly greater than that caused by phenylephrine (1.1-fold above baseline), an adrenergic agent that is a poor stimulator of adenylate cyclase. Prostaglandins E1 and E2, which are good stimulators of adenylate cyclase, caused striking disruption of the blood-ocular barriers, and prostaglandins that are not good stimulators of adenylate cyclase had little or no effect on these barriers. The magnitude of the prostaglandin E1 effect (9.3-fold above baseline) was similar to that of N-ethylcarboxamidoadenosine (NECA), the most potent adenosine agonist, and was greater than one would predict based on its effect on adenylate cyclase in vitro. Prostaglandin E1, like NECA, also caused retinal vasodilation and hemorrhages. These data suggest that stimulation of intracellular cyclic AMP accumulation may be a common feature of mediators that cause breakdown of the blood-retinal barrier, but there may be another as yet unexplained feature shared by PGE1 and NECA that makes them particularly effective and capable of causing retinal vasodilation and hemorrhages.
Sen
H A
HA
Department of Ophthalmology, University of Virginia Medical Center, Charlottesville 22908.
Campochiaro
P A
PA
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001813:Blood-Retinal Barrier / Q000187:drug effects*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000502:physiology*; D019793:Fluorescein; D005452:Fluoresceins; D015590:Fluorophotometry; D005654:Fundus Oculi; D011453:Prostaglandins / Q000494:pharmacology; D011817:Rabbits; D013566:Sympathomimetics / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014822:Vitreous Body / Q000187:drug effects
D005452:Fluoresceins; D011453:Prostaglandins; D013566:Sympathomimetics; D014665:Vasodilator Agents; D019830:Adenosine-5'-(N-ethylcarboxamide); D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000241:Adenosine; D019793:Fluorescein