Secretogranin III as a novel target for the therapy of choroidal neovascularization. (April 2019)

• Record Type: Journal Article
• Authors: LeBlanc, Michelle E.; Wang, Weiwen; Ji, Yanli; Tian, Hong; Liu, Dachuan; Zhang, Xuxiang; Li, Wei
• Is Part Of: Experimental eye research. Volume 181(2019)
• Page Start: 120
• Page End: 126
• Publication Date: 2019-04
• Subjects: Secretogranin III -- Scg3 -- Angiogenic factor -- Anti-angiogenic therapy -- Choroidal neovascularization -- CNV -- AMD; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2019.01.009
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: 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 Matrigel-induced 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. Highlights: Scg3 is a highly disease-selective angiogenic factor. Scg3 is a novel target for choroidal neovascularization (CNV). Scg3-neutralizing monoclonal antibody (mAb) alleviates laser-induced CNV. Scg3-neutralizing mAb ameliorates Matrigel-induced CNV.