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.
[1]Univ Miami, Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
[2]Univ Miami, Sch Med, Vasc Biol Inst, Miami, FL 33136 USA.
[3]Fudan Univ, Zhongshan Hosp, Dept Ophthalmol, Shanghai 200433, Peoples R China.
[4]Univ Nevada, Sch Life Sci, Las Vegas, NV 89154 USA.
[5]Zhengzhou Eye Hosp, Dept Ophthalmol, Zhengzhou 450000, Henan, Peoples R China.
[6]Xinxiang Med Univ, Sch Publ Hlth, Xinxiang 453003, Henan, Peoples R China.
[7]Everglades Biopharma, Miami, FL 33156 USA.
[8]Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
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