Tao Zhao1, Jie Zhang2, Yanyan Zhang3, Jingjing Huang3, Xin Wang2,3, Yingqian Zhang2, Ming Zhang4, Ye Yuan1, Kai Xiao2,3, Hongxia Li2, Zhihui Zhong2,3. 1. 1 Shandong Buchang Pharmaceutical Company , Heze, China . 2. 2 Laboratory of Nonhuman Primate Disease Modeling Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu, China . 3. 3 Sichuan Kangcheng Biotech Co., Inc., Chengdu, China . 4. 4 Department of Ophthalmology, West China Hospital, Sichuan University , Chengdu, China .
Abstract
PURPOSE: A study was conducted to evaluate the inhibitory effects of vascular endothelial growth factor receptor 2 (VEGFR2) monoclonal antibody, BC001, against laser-induced choroidal neovascularization (CNV). METHODS: We induced the experimental CNV in rhesus monkey eyes using laser photocoagulation. Monkeys were randomly assigned to 4 groups that received a single intravitreal administration of BC001 at 0 (vehicle-treated group), 0.05, 0.2, and 0.5 mg/eye. Fundus fluorescein angiography, optical coherence tomography, and histological studies were used for evaluations. The ocular recovery was determined by comparing changes of fluorescein leaking area and thickness of disrupted retina around the laser burn spot before and after drug administration. Choroidal blood vessels were stained and quantified by lectin staining. Hematoxylin and eosin staining was performed to determine the general histological complications. RESULTS: An intravitreal injection of BC001 at 0.05, 0.2, and 0.5 mg per eye at 20 days after laser burn significantly reduced the CNV-induced fluorescein leakage, retina pathology, and aberrant choroidal vessel growth and did not change intraocular pressure or induce any immune response. CONCLUSION: BC001 confers significant inhibitory effects against laser-induced CNV in rhesus monkeys, thereby suggesting that prevention of VEGFR2 activation may be promising as an alternative therapeutic target for exudative age-related macular degeneration.
PURPOSE: A study was conducted to evaluate the inhibitory effects of vascular endothelial growth factor receptor 2 (VEGFR2) monoclonal antibody, BC001, against laser-induced choroidal neovascularization (CNV). METHODS: We induced the experimental CNV in rhesus monkey eyes using laser photocoagulation. Monkeys were randomly assigned to 4 groups that received a single intravitreal administration of BC001 at 0 (vehicle-treated group), 0.05, 0.2, and 0.5 mg/eye. Fundus fluorescein angiography, optical coherence tomography, and histological studies were used for evaluations. The ocular recovery was determined by comparing changes of fluorescein leaking area and thickness of disrupted retina around the laser burn spot before and after drug administration. Choroidal blood vessels were stained and quantified by lectin staining. Hematoxylin and eosin staining was performed to determine the general histological complications. RESULTS: An intravitreal injection of BC001 at 0.05, 0.2, and 0.5 mg per eye at 20 days after laser burn significantly reduced the CNV-induced fluorescein leakage, retina pathology, and aberrant choroidal vessel growth and did not change intraocular pressure or induce any immune response. CONCLUSION: BC001 confers significant inhibitory effects against laser-induced CNV in rhesus monkeys, thereby suggesting that prevention of VEGFR2 activation may be promising as an alternative therapeutic target for exudative age-related macular degeneration.
Authors: Tu M Tran; Soohyun Kim; Kira H Lin; Sook Hyun Chung; Sangwan Park; Yevgeniy Sazhnyev; Yinwen Wang; David Cunefare; Sina Farsiu; Sara M Thomasy; Ala Moshiri; Glenn Yiu Journal: Invest Ophthalmol Vis Sci Date: 2020-07-01 Impact factor: 4.799