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Xin Rong, Hong Tian, Liu Yang, Wei Li; Secretogranin III is a diabetes-selective retinal vascular leakage factor. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2690.
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© ARVO (1962-2015); The Authors (2016-present)
Secretogranin III (Scg3) was recently reported as a diabetes-selective or restricted angiogenic factor that preferentially promotes corneal angiogenesis of diabetic but not healthy mice. Despite our recent finding of Scg3-neutralizing monoclonal antibody to alleviate retinal vascular leakage in diabetic mice, Scg3 activity to induce retinal vascular leakage has not been directly demonstrated in vivo. The purpose of this study is to characterize the activity of Scg3 to induce retinal vascular leakage in diabetic and healthy mice.
Streptozotocin (STZ) was intraperitoneally injected into C57BL/6 mice (male, 6 weeks old). Hyperglycemic mice were aged for 4 months to develop diabetic retinopathy. Scg3 (250 ng/1ml/eye) or VEGF (100 ng/1ml/eye) was intravitreally injected into one eye of diabetic or age-matched control mice with PBS for fellow eyes. Evans blue assay was performed 24 h post injection to quantify retinal leakage. Data were expressed as leakage indexes based on the amount of leaked Evans blue dye and analyzed by paired Student’s t-test.
The results showed that intravitreal injection of vascular endothelial growth factor (VEGF) induced retinal vascular leakage in healthy mice (6.13-fold increase, p<0.01; VEGF vs. PBS), consistent with previous reports that VEGF is a vascular permeability factor (VPF) in healthy and diseased vessels. However, intravitreally injected Scg3 failed to stimulate retinal vascular leakage in healthy mice (0.93-fold decrease, p>0.05). Interestingly, intravitreal injection of Scg3 induced robust retinal leakage in diabetic mice (6.33-fold increase, p<0.05; Scg3 vs. PBS), suggesting that Scg3 selectively promoted retinal vascular leakage only in diabetic but not healthy mice. These findings are consistent with our recent study, in which Scg3 was discovered as a highly disease-restricted endothelial ligand to selectively bind diabetic but not healthy retinal vessels.
Our results unambiguously established Scg3 as a novel vascular leakage factor (VLF) in an in vivo setting. In contrast to VEGF as a conventional vascular permeability factor, Scg3 is a diabetes-restricted VLF that selectively stimulates retinal vascular leakage in diabetic but not healthy mice. To our knowledge, Scg3 is the first VLF with such diabetes selectivity or restrictiveness.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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