A potential therapeutic strategy for inhibition of ocular neovascularization with a new endogenous protein: rhEDI-8t

作者:Zhang, Ling; Shen, Xi; Lu, Qing; Zhou, Qingwei; Gu, Jiaqi; Gan, Renbao; Zhang, Hui; Sun, Xiaodong; Xie, Bing*
来源:Graefes Archive for Clinical and Experimental Ophthalmology, 2012, 250(5): 731-739.
DOI:10.1007/s00417-011-1765-y

摘要

Endogenous angiogenesis inhibitors act as natural negative feedback in the focal area during the neovascularization process, and have less interference on physiological angiogenesis, and thus fewer negative side-effects. These inhibitors are potential candidates to combine with or substitutes for current popular anti-angiogenesis treatments to have synergistic effect. In this study, the effects of recombinant endothelial growth inhibitor protein (rhEDI-8t), a novel endogenous protein originated from collagen VIII, was investigated on ocular neovascularization (NV). Endostatin, a well-identified endogenous angiogenesis inhibitor, was compared in parallel and served as a positive control. @@@ The inhibitory effect of rhEDI-8t on vascular endothelial cells was evaluated by a human umbilical vascular endothelial cells (HUVEC) proliferation test and a bovine aortic endothelial cells (BAEC) migration experiment. The effect of rhEDI-8t on ocular NV was further investigated in mice with choroidal neovascularization (choroidal NV) induced by laser, ischemic retinopathy and transgenic mice with expression of VEGF in photoreceptors (rho/VEGF) respectively. @@@ RhEDI-8t inhibited the growth of HUVECs and migration of BAECs stimulated by basic fibroblast growth factor (bFGF). Mice intravitreally treated with rhEDI-8t showed a significant reduction of choroidal NV, retinal NV and subretinal NV. @@@ Endogenous angiogenesis inhibitor rhEDI-8t showed a potent anti-angiogenesis effect in both in vitro and in vivo experiments. It contributed to the suppression of ocular NV. The study suggested that rhEDI-8t could be a subsidiary potent therapeutic medicine in addition to anti-VEGF therapy in future clinical anti-angiogenesis treatment.