Himber J, de Burlet G, Andermann G
Alcon Research and Development, Kaysersberg, France.
J Ocul Pharmacol. 1989 Summer;5(2):93-8. doi: 10.1089/jop.1989.5.93.
Alpha-chymotrypsin-induced ocular hypertension in albino rabbits is widely used as an experimental model to screen potential antiglaucoma drugs. The present study compares the intraocular pressure (IOP) response following the ocular application of single or repeated adrenergic agents in conscious albino and pigmented rabbits. A single instillation of clonidine was not as effective in lowering the IOP in pigmented hypertensive rabbit eyes as in albino hypertensive eyes. Similarly, betaxolol moderately lowered the IOP in albino rabbits but induced a slight response when pigmented rabbits were used as an experimental model. Twice-a-day applications of betaxolol in pigmented hypertensive eyes permitted an identical level of IOP decrease to be reached, as observed in a one-day study in albino rabbits, after at least 6 days of treatment. It has been suggested that the pigmented layers of the iris-ciliary body may act as sites for topically applied antiglaucoma drugs. Non-specific binding could explain in part the frequent discrepancy observed between the preclinical results obtained in albino hypertensive rabbit eyes and clinical results obtained in glaucomatous human eyes.
α-糜蛋白酶诱导的白化兔高眼压被广泛用作筛选潜在抗青光眼药物的实验模型。本研究比较了在清醒的白化兔和有色兔眼内应用单次或重复肾上腺素能药物后眼压(IOP)的反应。单次滴注可乐定在降低有色高血压兔眼的眼压方面不如在白化高血压兔眼中有效。同样,倍他洛尔适度降低了白化兔的眼压,但在以有色兔作为实验模型时仅引起轻微反应。在有色高血压眼中每天两次应用倍他洛尔,在至少6天的治疗后,可达到与白化兔一天研究中观察到的相同程度的眼压降低。有人提出,虹膜睫状体的色素层可能是局部应用抗青光眼药物的作用部位。非特异性结合可以部分解释在白化高血压兔眼中获得的临床前结果与青光眼患者眼中获得的临床结果之间经常出现的差异。