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Wei Li, Michelle LeBlanc, Weiwen Wang, Yanli Ji, Dachuan Liu, Xuxiang Zhang, Hong Tian; Secretogranin III as a novel target for anti-angiogenic therapy of choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3266. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Secretogranin III (Scg3) was recently discovered as a highly disease-restricted angiogenic factor. Anti-Scg3 monoclonal antibody (mAb) has been demonstrated with high efficacy to treat diabetic retinopathy. The purpose of this study is to investigate whether Scg3 is also an angiogenic target for the therapy of choroidal neovascularization (CNV) in mouse models.
C57BL/6 mice (6 weeks old) were treated with laser photocoagulation to induce CNV on Day 0. Scg3-neutralizing polyclonal antibody (pAb) or mAb was intravitreally on Day 3. Vascular endothelial growth factor (VEGF) inhibitor aflibercept and control IgG were included as positive and negative controls, respectively. Fluorescein angiography was performed to analyze CNV leakage on Day 7. Eyecups were isolated on Day 8, fixed, stained with fluorescence-labeled isolectin B4 and quantified for CNV 3D volume, lesion area and vessel density using confocal microscopy. Furthermore, Matrigel was subretinally injected into mice to induce CNV on Day 0. Scg3-neutralizing pAb, mAb, aflibercept or control IgG was subcutaneously injected on Day 0, 2 and 4. Matrigel-induced CNV leakage was analyzed on Day 7 using fluorescein angiography. Signal intensity was quantified using ImageJ software.
Intravitreal injection of Scg3-neutralizing pAb or mAb significantly alleviated laser-induced CNV leakage (p<0.0001) with similar high efficacy to aflibercept. Scg3 pAb, mAb and aflibercept also markedly reduced CNV 3D volume, lesion area and vessel density (p<0.01). Additionally, subcutaneous administration of Scg3-neutralizing pAb or mAb significantly suppressed Matrigel-induced CNV (p<0.01). The efficacy of anti-Scg3 pAb or mAb was comparable to aflibercept for ameliorating Matrigel-induced CNV.
These results suggest that Scg3 may play an important role in CNV pathogenesis and that anti-Scg3 mAb can inhibit CNV in different disease models. Given that Scg3 is a highly disease-restricted angiogenic factor with no detectable binding or functional activity in normal vessels, anti-Scg3 therapy of CNV may have no adverse effects on normal vessels.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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