PURPOSE: To evaluate the preclinical safety of intravitreal bevacizumab, which is a full-length humanized monoclonal antibody against the vascular endothelial growth factor (VEGF), in rabbit eyes over a short-term period. METHODS: Twenty-four rabbits were divided into two groups, each with two subgroups. The first group (groups 1 and 2) received 1.25 mg (0.05 mL) intravitreal bevacizumab, and the second group (groups 3 and 4) received 3.00 mg (0.12 mL) intravitreal bevacizumab. The right eyes were designated as the study eyes, and the left eyes served as a control and received the same volume of saline intravitreally. Groups 1 and 3 were labeled as early groups and scheduled to be terminated at 14 days. Groups 2 and 4, labeled as late groups, were scheduled to be terminated at 28 days. Besides electroretinography (ERG) and visually evoked potentials (VEP), central corneal thickness, intraocular pressure, fundus photography, and anterior segment imaging were performed at baseline and scheduled time points. Enucleated eyes were preserved for light and electron microscopic investigation. RESULTS: No anterior segment inflammation was observed, except in one eye in group 1 which showed a uveitic reaction. No evidence of retinal toxicity was seen with intravitreal bevacizumab at doses of 1.25 and 3.00 mg, by either ERG or light microscopy. Electron microscopic assessment revealed mitochondrial damage in the inner segments of photoreceptors. Immunohistochemical staining with bax and caspase-3 and -9 showed intensive apoptotic protein expression in all study sections and minimal expression in the control eyes. CONCLUSIONS: Although electrophysiologic investigation and light microscopy showed normal retinal function and structure, mitochondrial disruption in the inner segments of photoreceptors was detected by electron microscopy, and apoptotic expression was detected after the injection of intravitreal bevacizumab.
PURPOSE: To evaluate the preclinical safety of intravitreal bevacizumab, which is a full-length humanized monoclonal antibody against the vascular endothelial growth factor (VEGF), in rabbit eyes over a short-term period. METHODS: Twenty-four rabbits were divided into two groups, each with two subgroups. The first group (groups 1 and 2) received 1.25 mg (0.05 mL) intravitreal bevacizumab, and the second group (groups 3 and 4) received 3.00 mg (0.12 mL) intravitreal bevacizumab. The right eyes were designated as the study eyes, and the left eyes served as a control and received the same volume of saline intravitreally. Groups 1 and 3 were labeled as early groups and scheduled to be terminated at 14 days. Groups 2 and 4, labeled as late groups, were scheduled to be terminated at 28 days. Besides electroretinography (ERG) and visually evoked potentials (VEP), central corneal thickness, intraocular pressure, fundus photography, and anterior segment imaging were performed at baseline and scheduled time points. Enucleated eyes were preserved for light and electron microscopic investigation. RESULTS: No anterior segment inflammation was observed, except in one eye in group 1 which showed a uveitic reaction. No evidence of retinal toxicity was seen with intravitreal bevacizumab at doses of 1.25 and 3.00 mg, by either ERG or light microscopy. Electron microscopic assessment revealed mitochondrial damage in the inner segments of photoreceptors. Immunohistochemical staining with bax and caspase-3 and -9 showed intensive apoptotic protein expression in all study sections and minimal expression in the control eyes. CONCLUSIONS: Although electrophysiologic investigation and light microscopy showed normal retinal function and structure, mitochondrial disruption in the inner segments of photoreceptors was detected by electron microscopy, and apoptotic expression was detected after the injection of intravitreal bevacizumab.
Authors: Xu Hou; Anil Kumar; Chunsik Lee; Bin Wang; Pachiappan Arjunan; Lijin Dong; Arvydas Maminishkis; Zhongshu Tang; Yang Li; Fan Zhang; Shi-Zhuang Zhang; Piotr Wardega; Sagarika Chakrabarty; Baoying Liu; Zhijian Wu; Peter Colosi; Robert N Fariss; Johan Lennartsson; Robert Nussenblatt; J Silvio Gutkind; Yihai Cao; Xuri Li Journal: Proc Natl Acad Sci U S A Date: 2010-06-21 Impact factor: 11.205
Authors: Anil Kumar; Xu Hou; Chunsik Lee; Yang Li; Arvydas Maminishkis; Zhongshu Tang; Fan Zhang; Harald F Langer; Pachiappan Arjunan; Lijin Dong; Zhijian Wu; Linda Y Zhu; Lianchun Wang; Wang Min; Peter Colosi; Triantafyllos Chavakis; Xuri Li Journal: J Biol Chem Date: 2010-03-15 Impact factor: 5.157
Authors: Suk Ho Byeon; Oh W Kwon; Ji Hun Song; Sung Eun Kim; Yong Sik Park Journal: Graefes Arch Clin Exp Ophthalmol Date: 2008-08-06 Impact factor: 3.117
Authors: Charles Q Yu; Min Zhang; Krisztina I Matis; Charles Kim; Mark I Rosenblatt Journal: Invest Ophthalmol Vis Sci Date: 2008-05-16 Impact factor: 4.799