机构：[1]Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, FL, USA[2]Vascular Biology Institute, University of Miami, Miami, FL, USA[3]Department of Ophthalmology, Zhengzhou Eye Hospital, Zhengzhou, Henan, China[4]Everlgades Biopharma, LLC, Miami, FL, USA[5]Department of Ophthalmology, Xuanwu Hospital, Beijing, China眼科首都医科大学宣武医院
Wet age-related macular degeneration (AMD) with choroidal neovascularization (CNV) is a leading cause of vision loss in the elderly. The advent of anti-vascular endothelial growth factor (VEGF) drugs represents a major breakthrough in wet AMD therapy but with limited efficacy to improve visual acuity. Secretogranin III (Scg3, SgIII) was recently discovered as a novel angiogenic factor with VEGF-independent mechanisms. Scg3-neutralizing monoclonal antibody (mAb) was reported to alleviate pathological retinal neovascularization in oxygen-induced retinopathy mice and retinal vascular leakage in diabetic mice with high efficacy and disease selectivity. Herein we investigated whether Scg3 is a novel angiogenic target for CNV therapy in mouse models. We found that anti-Scg3 ML49.3 mAb inhibited Scg3-induced proliferation and Src phosphorylation in human retinal microvascular endothelial cells. Intravitreal injection of Scg3-neutralizing polyclonal antibodies (pAb) or mAb significantly attenuated laser-induced CNV leakage, CNV 3D volume, lesion area and vessel density. Furthermore, subcutaneous administration of Scg3-neutralizing pAb or mAb significantly prevented Matrigelinduced CNV. The efficacy of anti-Scg3 pAb or mAb was comparable to VEGF inhibitor aflibercept. These findings suggest that Scg3 plays an important role in CNV pathogenesis and that anti-Scg3 mAb efficiently ameliorates laser- or Matrigel-induced CNV.
基金：
NIH [P30-EY014801, R01GM094449, R21HD075372, R21EY027065, R41EY027665]; American Diabetes Association [1-18IBS-172]; Research to Prevent Blindness (RPB); American Heart Association Predoctoral Fellowship [14PRE18310014, 16PRE27250308]; RPB
第一作者机构：[1]Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, FL, USA
共同第一作者：
通讯作者：
通讯机构：[*1]Bascom Palmer Eye Institute, University of Miami School of Medicine, 1638 NW 10th Avenue, Miami, FL, 33136, USA.
推荐引用方式(GB/T 7714)：
LeBlanc Michelle E.,Wang Weiwen,Ji Yanli,et al.Secretogranin III as a novel target for the therapy of choroidal neovascularization[J].EXPERIMENTAL EYE RESEARCH.2019,181:120-126.doi:10.1016/j.exer.2019.01.009.
APA：
LeBlanc, Michelle E.,Wang, Weiwen,Ji, Yanli,Tian, Hong,Liu, Dachuan...&Li, Wei.(2019).Secretogranin III as a novel target for the therapy of choroidal neovascularization.EXPERIMENTAL EYE RESEARCH,181,
MLA：
LeBlanc, Michelle E.,et al."Secretogranin III as a novel target for the therapy of choroidal neovascularization".EXPERIMENTAL EYE RESEARCH 181.(2019):120-126
