June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
The effect of anti-VEGF-A/Ang-2 bispecific antibody on murine retinal vein occlusion model
Author Affiliations & Notes
  • Aika Kuriyama
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
  • Shinsuke Nakamura
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
  • Yae Hidaka
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
  • Hiroto Abe
    Chugai Pharmaceutical Co., Ltd. Product Research Dept., Kanagawa, Japan
  • Koki Nagaoka
    Chugai Pharmaceutical Co., Ltd. Product Research Dept., Kanagawa, Japan
  • Yuta Inokuchi
    Chugai Pharmaceutical Co., Ltd. Product Research Dept., Kanagawa, Japan
  • Tetsuhiro Soeda
    Chugai Pharmaceutical Co., Ltd. Product Research Dept., Kanagawa, Japan
  • Masamitsu Shimazawa
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
  • Hideaki Hara
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
  • Footnotes
    Commercial Relationships   Aika Kuriyama None; Shinsuke Nakamura Chugai Pharmaceutical Co., Ltd., Code F (Financial Support); Yae Hidaka None; Hiroto Abe Chugai Pharmaceutical Co., Ltd., Code E (Employment); Koki Nagaoka Chugai Pharmaceutical Co., Ltd., Code E (Employment); Yuta Inokuchi Chugai Pharmaceutical Co., Ltd., Code E (Employment); Tetsuhiro Soeda Chugai Pharmaceutical Co., Ltd., Code E (Employment); Masamitsu Shimazawa Chugai Pharmaceutical Co., Ltd., Code F (Financial Support); Hideaki Hara Chugai Pharmaceutical Co., Ltd., Code F (Financial Support)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1775. doi:
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    • Get Citation

      Aika Kuriyama, Shinsuke Nakamura, Yae Hidaka, Hiroto Abe, Koki Nagaoka, Yuta Inokuchi, Tetsuhiro Soeda, Masamitsu Shimazawa, Hideaki Hara; The effect of anti-VEGF-A/Ang-2 bispecific antibody on murine retinal vein occlusion model. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1775.

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

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Abstract

Purpose : Macular edema and retinal ischemia cause vision loss in retinal vein occlusion (RVO) patients. Faricimab, a bispecific antibody that inhibits VEGF-A and angiopoietin-2 (Ang-2), improved visual acuity in patients with neovascular age-related macular degeneration and diabetic macular edema and extended the treatment interval up to 4 months [Lancet; 399(10326):729-740, 2022, Lancet; 399(10326):741-755, 2022). Moreover, a phase III trial in RVO patients is underway (BALATON/COMINO). Ang-2 is induced by hypoxia and inflammation and increases vascular permeability by causing vascular destabilization. In this study, we investigated the effects of mouse surrogate anti-VEGF-A, anti-Ang-2 and anti-VEGF-A /Ang-2 bispecific antibody (BsAb) using an RVO murine model.

Methods : Eight weeks old male ddY mice were injected with Rose Bengal, and then three retinal veins were occluded by laser irradiation at 50 mW power, 50 µm size, and 5 seconds duration. The expression levels of mRNA and protein in the retinas of the RVO murine model were evaluated by RNA-seq analysis and Western blotting, respectively. Mouse cross-reactive tool antibodies, anti-VEGF-A antibody (200 µg/mL), anti-Ang-2 antibody (200 µg/mL), and BsAb (400 µg/mL) were injected into the vitreous body of the right eyes (2 μL) immediately after laser irradiation. Retinal edema was evaluated by measures the thinning of the inner nuclear layer. The visual function was evaluated by the electroretinogram (ERG). TUNEL staining was used to measure cell apoptosis.

Results : In this model, we observed the increase in mRNA levels of VEGF-A and Ang-2 in the retinas after occlusion, and also confirmed the increase in protein level of Ang-2 and the decrease of Tie-2. BsAb tended to suppress retinal edema formation as much as anti-VEGF-A antibody and anti-Ang-2 antibody at 1day. In the case of ERG, BsAb tended to suppress a- and b-wave amplitude reduction at 1, 7, and 14 days after occlusion compared to anti-VEGF-A antibody and anti-Ang-2 antibody. Moreover, both anti-Ang-2 antibody and BsAb significantly inhibited cell death in the retina at day 1.

Conclusions : We show that Ang-2 mRNA and protein levels are upregulated in this laser induced murine model of RVO. Inhibition of Ang-2 as well as dual inhibition of Ang-2 and VEGF-A had effects on retinal edema suppression, retinal function as well as cell death reduction.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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