Secretogranin III as a disease-associated ligand for antiangiogenic therapy of diabetic retinopathy.
Michelle E LeBlancWeiwen WangXiuping ChenNora B CaberoyFeiye GuoChen ShenYanli JiHong TianHui WangRui ChenWei LiPublished in: The Journal of experimental medicine (2017)
Diabetic retinopathy (DR) is a leading cause of vision loss with retinal vascular leakage and/or neovascularization. Current antiangiogenic therapy against vascular endothelial growth factor (VEGF) has limited efficacy. In this study, we applied a new technology of comparative ligandomics to diabetic and control mice for the differential mapping of disease-related endothelial ligands. Secretogranin III (Scg3) was discovered as a novel disease-associated ligand with selective binding and angiogenic activity in diabetic but not healthy vessels. In contrast, VEGF bound to and induced angiogenesis in both diabetic and normal vasculature. Scg3 and VEGF signal through distinct receptor pathways. Importantly, Scg3-neutralizing antibodies alleviated retinal vascular leakage in diabetic mice with high efficacy. Furthermore, anti-Scg3 prevented retinal neovascularization in oxygen-induced retinopathy mice, a surrogate model for retinopathy of prematurity (ROP). ROP is the most common cause of vision impairment in children, with no approved drug therapy. These results suggest that Scg3 is a promising target for novel antiangiogenic therapy of DR and ROP.
Keyphrases
- diabetic retinopathy
- vascular endothelial growth factor
- optical coherence tomography
- endothelial cells
- high glucose
- type diabetes
- wound healing
- stem cells
- magnetic resonance
- diabetic rats
- oxidative stress
- high resolution
- emergency department
- bone marrow
- drug induced
- metabolic syndrome
- cell therapy
- high density
- mass spectrometry
- smoking cessation
- replacement therapy
- optic nerve
- dengue virus
- contrast enhanced