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Title: Preclinical safety evaluation of intravitreal injection of full-length humanized vascular endothelial growth factor antibody in rabbit eyes
Authors: Kuşbeci, Tuncay
İnan, Ümit Ubeyt
Uludağ Üniversitesi/Tıp Fakültesi/Histoloji ve Embriyoloji Anabilim Dalı.
Avcı, Berrin
Kaderli, Berkant
Avcı, Remzi
Temel, Şehime
Keywords: Coherence tomography findings
Bevacizumab avastin treatment
Iris neovascularization
Macular edema
Issue Date: Apr-2007
Publisher: Association of Research Vision Ophthalmology
Citation: İnan, U. U. vd. (2007). "Preclinical safety evaluation of intravitreal injection of full-length humanized vascular endothelial growth factor antibody in rabbit eyes". Investigative Ophthalmology & Visual Science, 48(4), 1773-1781.
Abstract: 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 eves 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 eves 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 bevacizurnab.
ISSN: 01460404
Appears in Collections:PubMed
Web of Science

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