Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1029-1047 |
| Number of pages | 19 |
| Journal | Journal of Experimental Medicine |
| Volume | 214 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2017 |
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ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Secretogranin III as a disease-associated ligand for antiangiogenic therapy of diabetic retinopathy. / LeBlanc, Michelle E.; Wang, Weiwen; Chen, Xiuping; Caberoy, Nora B.; Guo, Feiye; Shen, Chen; Ji, Yanli; Tian, Hong; Wang, Hui; Chen, Rui; Li, Wei.
In: Journal of Experimental Medicine, Vol. 214, No. 4, 01.04.2017, p. 1029-1047.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Secretogranin III as a disease-associated ligand for antiangiogenic therapy of diabetic retinopathy
AU - LeBlanc, Michelle E.
AU - Wang, Weiwen
AU - Chen, Xiuping
AU - Caberoy, Nora B.
AU - Guo, Feiye
AU - Shen, Chen
AU - Ji, Yanli
AU - Tian, Hong
AU - Wang, Hui
AU - Chen, Rui
AU - Li, Wei
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20161802
DO - 10.1084/jem.20161802
M3 - Article
C2 - 28330905
AN - SCOPUS:85021901880
VL - 214
SP - 1029
EP - 1047
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 4
ER -