Sen H A, Campochiaro P A
Department of Ophthalmology, University of Virginia Medical Center, Charlottesville 22908.
Invest Ophthalmol Vis Sci. 1991 Jun;32(7):2006-10.
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.
给有色素的兔子玻璃体内注射0.1毫升不同浓度的受试药物，并在注射后6小时和24小时进行玻璃体液荧光光度测定。二丁酰环磷腺苷（AMP）和8-溴环磷腺苷仅在相对高浓度时引起可逆性玻璃体内荧光素渗漏。作为腺苷酸环化酶有效刺激剂的肾上腺素能药物（肾上腺素、异丙肾上腺素和去甲肾上腺素）引起短暂性玻璃体内荧光素渗漏（比基线高2.3 - 3.1倍），显著大于苯肾上腺素（比基线高1.1倍）引起的渗漏，苯肾上腺素是一种对腺苷酸环化酶刺激作用较弱的肾上腺素能药物。作为腺苷酸环化酶良好刺激剂的前列腺素E1和E2引起血眼屏障的显著破坏，而对腺苷酸环化酶刺激作用不佳的前列腺素对这些屏障几乎没有影响。前列腺素E1的作用幅度（比基线高9.3倍）与最有效的腺苷激动剂N - 乙基羧酰胺腺苷（NECA）相似，且大于根据其体外对腺苷酸环化酶的作用所预测的幅度。与NECA一样，前列腺素E1也引起视网膜血管扩张和出血。这些数据表明，细胞内环磷腺苷积累的刺激可能是导致血视网膜屏障破坏的介质的一个共同特征，但前列腺素E1和NECA可能还有另一个尚未解释的共同特征，使其特别有效并能够引起视网膜血管扩张和出血。
