July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
PDGFRβ blockade inhibits choroidal neovascularization and fibrosis in a laser-induced CNV model in mice
Author Affiliations & Notes
  • Ye Liu
    Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, HOKKAIDO, Japan
  • Kousuke Noda
    Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, HOKKAIDO, Japan
  • Di Wu
    Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, HOKKAIDO, Japan
  • Miyuki Murata
    Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, HOKKAIDO, Japan
  • Atsuhiro Kanda
    Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, HOKKAIDO, Japan
  • Susumu Ishida
    Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, HOKKAIDO, Japan
  • Footnotes
    Commercial Relationships   Ye Liu, None; Kousuke Noda, Novartis Pharma AG (F); Di Wu, None; Miyuki Murata, None; Atsuhiro Kanda, None; Susumu Ishida, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 56. doi:
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      Ye Liu, Kousuke Noda, Di Wu, Miyuki Murata, Atsuhiro Kanda, Susumu Ishida; PDGFRβ blockade inhibits choroidal neovascularization and fibrosis in a laser-induced CNV model in mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):56.

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

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Abstract

Purpose : Anti-vascular endothelial growth factor (VEGF) agents have revolutionized the treatment of wet age-related macular degeneration (AMD). However, it has been recently reported that subretinal fibrosis develops approximately in half of all anti-VEGF-treated cases within 2 years and is associated with poor visual prognosis. Therefore, it is necessary to develop a novel therapeutic approach to treat both choroidal neovascularization (CNV) and subretinal fibrosis. The purpose of this study is to investigate whether blockade for platelet-derived growth factor receptor β (PDGFRβ) inhibits the formation of CNV and fibrosis in a laser-induced CNV model in mice.

Methods : CNV was generated by laser photocoagulation (532nm, 180mW, 75μm) in male C57BL/6J mice aged 6-8 weeks. PDGFRβ neutralizing antibody or isotype-matched control antibody was injected into the vitreous cavity immediately after laser photocoagulation. Retinal pigment epithelium (RPE)-choroid flatmounts were harvested and stained with isolectin B4 and anti-mouse type I collagen antibody to measure the size of CNV and fibrosis, respectively, at days 7 and 21. RPE-choroid complex was also harvested 3 days after laser injury and the mRNA level of Acta2 (gene symbol for α-SMA) was analyzed by real-time qPCR.

Results : PDGFRβ blockade attenuated the size of CNV and fibrosis (CNV, 8332±2240.7µm2; fibrosis, 7154.2±1859.1µm2) compared to the control (CNV, 13033.7±3092.8µm2; fibrosis, 11078.1±3714.3µm2, n=8, p<0.01) at 7 days after laser injury. At 21 days after laser photocoagulation, PDGFRβ blockade suppressed the size of fibrosis (5655±1471.7µm2), compared to the control (10717±3628.9µm2, n=6, p<0.01). Real-time qPCR showed that PDGFRβ blockade inhibited the upregulation of Acta2 expression 3 days after laser injury by 37.5% (n=6, p<0.01).

Conclusions : The current data suggest that PDGFRβ is an attractive molecular target in the prevention of subretinal fibrosis in 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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