Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.