Passos Elke, Genaidy Mahmoud M, Peyman Gholam A
Department of Ophthalmology, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
Ophthalmic Surg Lasers. 2002 Mar-Apr;33(2):140-4.
To investigate the ocular toxicity of intravitreally administered tacrolimus, a drug with potent immunosuppressive activity.
To evaluate toxicity, tacrolimus was injected into the midvitreous cavity of 20 eyes of New Zealand pigmented rabbits at concentrations of 10, 50, 100, 250, 500, and 1000 microg. Control eyes received balanced salt solution. Eyes receiving 1000 microg were given injections of 0.2 mL solution; all others, including controls, received 0.1 mL. Rabbits were examined before the injections by slit-lamp biomicroscopy, indirect ophthalmoscopy, and an electroretinography test (ERG) was performed. The animals were followed up to 14 days postinjection by clinical examination and ERG. The animals were killed and the eyes were enucleated and processed for light microscopy.
No evidence of a retinal toxic reaction was seen in the eyes receiving 10 or 50 microg of tacrolimus. One out of 4 eyes that received 100 microg of the drug developed a vitreous reaction. All eyes treated with 250 microg or more developed vitreous reaction. One eye injected with 1000 microg of the drug developed occlusion of the temporal retinal vessels. Electroretinography showed decreasing b-wave amplitude with both dark- and light-adapted stimulus in the 500 and 1000 microg groups, and it was normal in the other groups. Histopathologic sections showed mild disorganization of the retina only at the 500 and 1000 microg dosage.
Doses of 10 and 50 microg of tacrolimus are nontoxic to rabbit eyes. Only transient vitreous opacities were observed in the groups that received 100 and 250 microg. Intravitreal doses of 500 and 1000 microg of tacrolimus proved to be toxic to the retina.
研究玻璃体内注射具有强效免疫抑制活性的药物他克莫司的眼毒性。
为评估毒性，将他克莫司以10、50、100、250、500和1000微克的浓度注入20只新西兰有色家兔的玻璃体内腔中部。对照眼注射平衡盐溶液。接受1000微克的眼注射0.2毫升溶液；其他所有组，包括对照组，均注射0.1毫升。在注射前通过裂隙灯生物显微镜检查、间接检眼镜检查对家兔进行检查，并进行视网膜电图测试（ERG）。在注射后对动物进行长达14天的临床检查和ERG随访。处死动物，摘除眼球并进行光镜检查。
接受10或50微克他克莫司的眼中未发现视网膜毒性反应的证据。接受100微克该药物的4只眼中有1只出现玻璃体反应。所有接受250微克或更高剂量治疗的眼均出现玻璃体反应。1只注射1000微克该药物的眼出现颞侧视网膜血管闭塞。视网膜电图显示，在500和1000微克组中，暗适应和光适应刺激下的b波振幅均降低，而其他组正常。组织病理学切片显示，仅在500和1000微克剂量时视网膜有轻度结构紊乱。
10和50微克剂量的他克莫司对兔眼无毒。在接受100和250微克的组中仅观察到短暂的玻璃体混浊。玻璃体内注射500和1000微克他克莫司对视网膜有毒性。
