July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
A novel bispecific inhibitor targeting VEGF and complement system suppressed angiogenesis in model of neovascular age-related macular degeneration
Author Affiliations & Notes
  • Shiqi Yang
    Department of Ophthalmology, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Tong Li
    Department of Ophthalmology, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Xueting Luo
    Department of Ophthalmology, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Xiaodong Sun
    Department of Ophthalmology, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Footnotes
    Commercial Relationships   Shiqi Yang, None; Tong Li, None; Xueting Luo, None; Xiaodong Sun, None
  • Footnotes
    Support   National Nature Science Foundation of China (81730026)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 67. doi:
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    • Get Citation

      Shiqi Yang, Tong Li, Xueting Luo, Xiaodong Sun; A novel bispecific inhibitor targeting VEGF and complement system suppressed angiogenesis in model of neovascular age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):67.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : We aimed to explore the therapeutic efficacy of IBI302 in neovascular age-related macular degeneration (AMD), which is a bispecific fusion protein targeting both the VEGF and complement system, in vitro and in vivo.

Methods : In vitro, the antiangiogenic potential of IBI302, aflibercept (VEGF antagonist), CID (complement inhibitor) or PBS (vehicle control) was evaluated in VEGF-stimulated human umbilical vein endothelial cells (HUVECs) by proliferation, migration, and tube formation assays. In vivo, after evaluating retinal toxicity by retinal histology and electroretinography, choroidal neovascularization (CNV) was induced by laser photocoagulation. IBI302, aflibercept, CID or PBS was administered through intravitreal injection immediately after laser. CNV leakage was observed by fundus fluorescein angiography (FFA), CNV area was measured in choroid flat mounts, and CNV thickness was evaluated by histological analyses in groups with different administration 3 days or 7 days after laser. Immunofluorescence, enzyme linked immunosorbent assay or western blot was performed to clarify the activation of complement system and evaluate the expression of pro-angiogenic factors and pro-inflammatory cytokines.

Results : In vitro, both IBI302 and aflibercept notably inhibited VEGF-induced proliferation, migration and tube formation of HUVECs. IBI302 had superior inhibitory effect on proliferation and similar inhibitory effect on migration or tube formation compared with aflibercept. In vivo, intravitreal injection of IBI302 did not show retinal toxicity, and meanwhile IBI302 administration exhibited the lowest fluorescein intensity score, the smallest CNV area, and the thinnest CNV lesion compared with aflibercept, CID or PBS in the laser-induced CNV model. Furthermore, IBI302 diminished the deposition of C3d, reduced the level of C5a and suppressed the formation of membrane attack complex (MAC) to effectively inhibit complement system activation. IBI302 regulates multiple critical components of CNV, including angiogenesis, inflammation and fibrosis, which prominently reduced the expression of VEGF, IL-1β, IL-18, COX-2, and TFG-β2.

Conclusions : IBI302, targeting both the VEGF and complement system, plays a multitargeted inhibitory role in CNV and might be considered as a promising therapeutic candidate for the treatment of neovascular AMD.

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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