Fortes Filho João Borges, Maia Mauricio, Tartarella Marcia Beatriz, Meyer Fabíola Schons, Fortes Bárbara Gastal Borges, Kliemann Lúcia Maria
Department of Ophthalmology, Medical School, Federal University of Rio Grande do Sul and Hospital de Clínicas de Porto Alegre, Porto Alegre (RS) 90035-903, Brazil.
Department of Ophthalmology, Medical School, Federal University of São Paulo, São Paulo (SP) 040023-062, Brazil.
Int J Ophthalmol. 2014 Jun 18;7(3):437-40. doi: 10.3980/j.issn.2222-3959.2014.03.09. eCollection 2014.
To evaluate histopathological retinal and renal response after one single dose of intravitreous injection of antiangiogenic drugs ranibizumab and bevacizumab in rats.
Experimental study in 60d of life adults Wistar rats. Ten animals were included. Group 1 included 5 animals that were injected with 1 µL ranibizumab 1.25 mg in the right eye and with 1 µL of balanced salt solution (BSS) in the left eye, as control; Group 2 included 5 animals that were injected with 1 µL of bevacizumab in the right eye and with 1 µL of BSS in the fellow eye. All injections were performed with Hamilton syringes. After 15d of the interventions, all animals were sacrificed in CO2 chamber. Both eyes were enucleated and one kidney was removed, fixed and embedded in paraffin for histopathological analysis by optic microscopy. For statistical purposes the initial expected abnormal histopathological responses were defined as 0%.
Atypical histopathological retinal response was detected in 2 eyes injected with ranibizumab (40%) as well as in 2 control eyes in group 1. Same was detected in 1 eye injected with bevacizumab (20%) as well as in 1 control eye, in group 2. The noted atypical findings were lymphocytes and eosinophils in the vitreous posterior cavity and mild retinal inflammatory reaction with ganglion cell layer edema but without clinical significance. No atypical histopathological renal response was detected.
Unexpected atypical histopathological retinal response without clinical significance was observed in 3 eyes injected with antiangiogenic drugs (2 in group 1 and 1 in group 2) as well as in 3 control eyes (2 in group 1 and 1 in group 2). No atypical renal response was detected suggesting no extra ocular involvement of the intravitreous injected antiangiogenic drugs.
评估大鼠单次玻璃体内注射抗血管生成药物雷珠单抗和贝伐单抗后视网膜和肾脏的组织病理学反应。
对60日龄成年Wistar大鼠进行实验研究。纳入10只动物。第1组包括5只动物,右眼注射1μL 1.25mg雷珠单抗,左眼注射1μL平衡盐溶液(BSS)作为对照;第2组包括5只动物,右眼注射1μL贝伐单抗,对侧眼注射1μL BSS。所有注射均使用汉密尔顿注射器。干预15天后,所有动物在二氧化碳舱中处死。摘除双眼并切除一侧肾脏,固定后石蜡包埋,通过光学显微镜进行组织病理学分析。为统计目的,最初预期的异常组织病理学反应定义为0%。
在注射雷珠单抗的2只眼中(40%)以及第1组的2只对照眼中检测到非典型组织病理学视网膜反应。在注射贝伐单抗的1只眼中(20%)以及第2组的1只对照眼中也检测到同样情况。观察到的非典型表现为玻璃体后腔中的淋巴细胞和嗜酸性粒细胞以及伴有神经节细胞层水肿的轻度视网膜炎症反应,但无临床意义。未检测到非典型组织病理学肾脏反应。
在注射抗血管生成药物的3只眼中(第1组2只,第2组1只)以及3只对照眼中(第1组2只,第2组1只)观察到无临床意义的意外非典型组织病理学视网膜反应。未检测到非典型肾脏反应,提示玻璃体内注射的抗血管生成药物无眼外累及。