Intravitreous injection of adenosine or its agonists causes breakdown of the blood-retinal barrier
H. A. Sen and P. A. Campochiaro
Department of Ophthalmology, University of Virginia School of Medicine, Charlottesville 22908.
Pigmented rabbits were anesthetized and given an intravitreous injection of
0.1 mL of a test substance or vehicle alone. Vitreous fluorophotometry was
performed before injections and at various time points after injections.
Compared with pretreatment scans, vehicle-injected eyes showed no change in
intravitreous fluorescein sodium leakage at 6 and 24 hours after injection.
Injection of adenosine (10(-2) mol/L) resulted in fluorescein leakage that
was significantly greater than that which occurred in control eyes at 6
hours after injection, but returned to baseline at 24 hours. This effect
was significantly attenuated by an adenosine receptor antagonist
(BW-A1433U), suggesting that it was mediated by specific adenosine
receptors. A nonselective adenosine receptor agonist,
N-ethylcarboxamidoadenosine, and two relatively A1 selective receptor
agonists, N6-cyclopentyladenosine and N6-phenylisopropyladenosine, also
caused dose-dependent intravitreous fluorescein leakage. The relative order
of potency was N-ethylcarboxamidoadenosine much greater than
N6-phenylisopropyladenosine, which was greater than
N6-cyclopentyladenosine, implicating A2 adenosine receptors. Intravitreous
injection of dipyridamole, an adenosine uptake inhibitor, caused enhanced
fluorescein leakage, presumably from extracellular accumulation of
endogenous adenosine. The results of this study suggest that adenosine may
be a mediator of blood-retinal barrier breakdown.
