Gal-Or Orly, Dotan Assaf, Dachbash Mor, Tal Kfir, Nisgav Yael, Weinberger Dov, Ehrlich Rita, Livnat Tami
Department of Ophthalmology, Rabin Medical Center, Petach Tikva, Israel.
Eye Research Laboratory, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, Israel.
Exp Eye Res. 2016 Apr;145:412-416. doi: 10.1016/j.exer.2016.02.006. Epub 2016 Feb 26.
Antivascular endothelial growth factor (Anti-VEGF) agents have been widely used for a variety of ocular disorders. The etiology of sustained ocular hypertension following intravitreal administration of anti-VEGF agents is yet to be unraveled. Our study investigates and characterizes the presence of intravitreally injected bevacizumab in the aqueous outflow channels of a rat model. Choroidal neovascularization (CNV) was induced by diode laser photocoagulation to the right eye of twelve Brown Norway rats. Bevacizumab (25 mg/ml) was injected intravitreally after 3 days. Immediately after bevacizumab injection, and 3, 6, 24 and 48 h later, animals were euthanized for immunofluorescence staining. Donkey anti-human IgG labeled with Alexa Fluor(®) 488 was used for bevacizumab immunoreactivity detection. Anti-CD31 antibody was used as a marker for Schlemm's canal endothelial cells. Untreated eyes were used as negative controls. The intensity of the immunostaining was analyzed qualitatively. Bevacizumab immunoreactivity was found in the aqueous outflow channels including the trabecular meshwork and Schlemm's canal immediately after injection, and declined incrementally within the following hours. Forty-eight hours after the injection, no bevacizumab staining was detected in the aqueous outflow channel structures. Our manuscript demonstrates the presence of bevacizumab in the trabecular meshwork and Schlemm's canal structures after intravitreal injection in a CNV induced rat model. Bevacizumab molecules passed through the aqueous outflow channels within 48 h after intravitreal bevacizumab injection.
抗血管内皮生长因子（Anti-VEGF）药物已被广泛用于多种眼部疾病。玻璃体内注射抗VEGF药物后持续性高眼压的病因尚未明确。我们的研究调查并描述了大鼠模型房水流出通道中玻璃体内注射的贝伐单抗的存在情况。通过二极管激光光凝诱导12只棕色挪威大鼠右眼脉络膜新生血管（CNV）。3天后玻璃体内注射贝伐单抗（25mg/ml）。在注射贝伐单抗后立即以及3、6、24和48小时后，对动物实施安乐死以进行免疫荧光染色。用Alexa Fluor(®) 488标记的驴抗人IgG用于检测贝伐单抗免疫反应性。抗CD31抗体用作施莱姆管内皮细胞的标志物。未治疗的眼睛用作阴性对照。对免疫染色强度进行定性分析。注射后立即在包括小梁网和施莱姆管在内的房水流出通道中发现贝伐单抗免疫反应性，并在随后的数小时内逐渐下降。注射后48小时，在房水流出通道结构中未检测到贝伐单抗染色。我们的论文证明了在CNV诱导的大鼠模型中玻璃体内注射后小梁网和施莱姆管结构中存在贝伐单抗。玻璃体内注射贝伐单抗后，贝伐单抗分子在48小时内通过房水流出通道。
