Suppression of Corticosteroid-Induced Ocular Hypertension in Sheep by Anecortave
Suppression of Corticosteroid-Induced Ocular Hypertension in Sheep by Anecortave
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DOI：
10.1001/archophthalmol.2009.387
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发表时间：
2010-03-01
影响因子：
--
通讯作者：
Podos, Steven M.
中科院分区：
文献类型：
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作者：
Candia, Oscar A.;Gerometta, Rosana;Podos, Steven M.
目的：探讨醋酸醋酸酯对类固醇性高眼压模型的降压作用。正常羊的眼睛表现出强烈的类固醇诱导的眼高血压反应。最近在一项不受控制的介入性病例系列中观察表明，在一小部分青光眼患者的眼睛中，作为亚tenon仓库给药时，anecortave引起了降压作用。方法：采用珀金眼压计监测16只正常羊的眼压，每日3次，双眼局部注射0.5%醋酸泼尼松龙，使眼压在12天内翻倍。一半的羊在开始双侧泼尼松龙注射前在1只眼睛接受了单侧的anecortave亚腱注射，而其余8只羊在泼尼松龙注射后IOP最大程度升高后接受了单侧的anecortave亚腱注射。结果：在这两组实验中，anecortave库的存在抑制了类固醇引起的IOP升高，并将升高的IOP恢复到基线水平。水流出设施的测量表明，用强的松龙加anecortave治疗的眼睛的流出设施比单独使用强的松龙的眼睛高5.8倍，这表明anecortave阻止了皮质类固醇产生的流出阻力的增加。结论：阐明anecortave在动物模型中的作用机制可能有助于设计治疗原发性开角型青光眼的新型干预措施。
Objective: To confirm the ocular hypotensive effects of anecortave acetate on an ovine model for steroid-induced ocular hypertension. Eyes of normal sheep exhibit a robust steroid-induced ocular hypertensive response. Recent observations in an uncontrolled, interventional case series indicated that anecortave elicited hypotensive effects when administered as a sub-Tenon depot in the eyes of a small sample of patients with glaucoma.Methods: Intraocular pressure (IOP) was monitored by Perkins applanation tonometry in 16 normal sheep receiving topically administered prednisolone acetate, 0.5%, in both eyes, 3 times daily, a protocol that doubled IOP within 12 days. Half of the sheep had received a unilateral sub-Tenon injection of anecortave in 1 eye prior to the initiation of the bilateral prednisolone instillations, while the 8 remaining sheep received the unilateral anecortave sub-Tenon depot after the IOP was maximally elevated by the prednisolone instillations.Results: In these 2 sets of experiments, the presence of the anecortave depot suppressed the steroid-induced IOP elevation and reverted the elevated IOP to baseline levels. Measurements of aqueous outflow facility indicated that eyes treated with prednisolone plus anecortave exhibited a 5.8-fold higher outflow facility than the fellow eyes solely exposed to prednisolone, indicating that anecortave prevented the increase in outflow resistance produced by the corticosteroid.Conclusion: Elucidation of the mechanisms of action of anecortave in animal models may prove relevant to the design of novel interventions for the management of primary open-angle glaucoma.