Secretogranin III as a novel target for the therapy of choroidal neovascularization

Michelle E. LeBlanc, Weiwen Wang, Yanli Ji, Hong Tian, Dachuan Liu, Xuxiang Zhang, Wei Li

Research output: Contribution to journalArticle

Abstract

Wet age-related macular degeneration (AMD) with choroidal neovascularization (CNV) is a leading cause of vision loss in the elderly. The advent of anti-vascular endothelial growth factor (VEGF) drugs represents a major breakthrough in wet AMD therapy but with limited efficacy to improve visual acuity. Secretogranin III (Scg3, SgIII) was recently discovered as a novel angiogenic factor with VEGF-independent mechanisms. Scg3-neutralizing monoclonal antibody (mAb) was reported to alleviate pathological retinal neovascularization in oxygen-induced retinopathy mice and retinal vascular leakage in diabetic mice with high efficacy and disease selectivity. Herein we investigated whether Scg3 is a novel angiogenic target for CNV therapy in mouse models. We found that anti-Scg3 ML49.3 mAb inhibited Scg3-induced proliferation and Src phosphorylation in human retinal microvascular endothelial cells. Intravitreal injection of Scg3-neutralizing polyclonal antibodies (pAb) or mAb significantly attenuated laser-induced CNV leakage, CNV 3D volume, lesion area and vessel density. Furthermore, subcutaneous administration of Scg3-neutralizing pAb or mAb significantly prevented Matrigel-induced CNV. The efficacy of anti-Scg3 pAb or mAb was comparable to VEGF inhibitor aflibercept. These findings suggest that Scg3 plays an important role in CNV pathogenesis and that anti-Scg3 mAb efficiently ameliorates laser- or Matrigel-induced CNV.

Original languageEnglish (US)
Pages (from-to)120-126
Number of pages7
JournalExperimental Eye Research
Volume181
DOIs
StatePublished - Apr 1 2019

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Choroidal Neovascularization
Monoclonal Antibodies
Neutralizing Antibodies
Vascular Endothelial Growth Factor A
Macular Degeneration
Therapeutics
Lasers
Pathologic Neovascularization
Retinal Neovascularization
Retinal Vessels
Intravitreal Injections
Angiogenesis Inducing Agents
secretogranin III
Visual Acuity
Endothelial Cells
Phosphorylation
Oxygen
Antibodies
Pharmaceutical Preparations

Keywords

  • AMD
  • Angiogenic factor
  • Anti-angiogenic therapy
  • Choroidal neovascularization
  • CNV
  • Scg3
  • Secretogranin III

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Secretogranin III as a novel target for the therapy of choroidal neovascularization. / LeBlanc, Michelle E.; Wang, Weiwen; Ji, Yanli; Tian, Hong; Liu, Dachuan; Zhang, Xuxiang; Li, Wei.

In: Experimental Eye Research, Vol. 181, 01.04.2019, p. 120-126.

Research output: Contribution to journalArticle

LeBlanc, Michelle E. ; Wang, Weiwen ; Ji, Yanli ; Tian, Hong ; Liu, Dachuan ; Zhang, Xuxiang ; Li, Wei. / Secretogranin III as a novel target for the therapy of choroidal neovascularization. In: Experimental Eye Research. 2019 ; Vol. 181. pp. 120-126.
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