Preliminary in vitro and in vivo assessment of a new targeted inhibitor for choroidal neovascularization in age-related macular degeneration
Preliminary in vitro and in vivo assessment of a new targeted inhibitor for choroidal neovascularization in age-related macular degeneration
Blog Article
Wenbo Li,1,* Lijie Dong,1,* Minwang Ma,2,* Bojie Hu,1 Zhenyu Lu,3 Xun Liu,1 Juping Liu,1 Xiaorong Li1 1Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China; 2Affiliated Hospital of Medical College of Chinese People’s Armed Police Forces (CapF), Tianjin, People’s Republic of China; 3Tianjin Precision Cell Biotechnology Co.Ltd., Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Choroidal neovascularization (CNV) in age-related macular degeneration usually causes blindness.We established a novel targeted inhibitor for CNV in age-related macular degeneration.The inhibitor CR2-sFlt 1 comprises a CR2-targeting fragment and an anti-vascular endothelial growth factor (VEGF) domain (sFlt 1).
The targeting of CR2-sFlt 1 was studied using the transwell assay in vitro and frozen sections in ACTIVE B COMPLEX vivo using green fluorescent labeling.Transwell assay results showed that CR2-sFlt 1 migrated to the interface of complement activation products and was present in the retinal tissue of the CR2-sFlt 1-treated CNV mice.Treatment effects were assessed by investigating the VEGF concentration in retinal pigmented epithelial cell medium and the thickness of the CNV complex in the mice treated with CR2-sFlt 1.CR2-sFlt 1 significantly reduced the VEGF secretion from retinal pigmented epithelial cells in vitro and Lacrosse Head retarded CNV progress in a mouse model.Expression analysis of VEGF and VEGFRs after CR2-sFlt 1 intervention indicated the existence of feedback mechanisms in exogenous CR2-sFlt 1, endogenous VEGF, and VEGFR interaction.
In summary, we demonstrated for the first time that using CR2-sFlt 1 could inhibit CNV with clear targeting and high selectivity.Keywords: choroidal neovascularization, macular degeneration, complement activation, vascular endothelial growth factor.