July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Anti-angiogenic and anti-scarring dual action of an anti-Fibroblast Growth Factor-2 aptamer in animal models of retinal disease
Author Affiliations & Notes
  • Robert B Bhisitkul
    Ophthalmology, University California-San Francisco, San Francisco, California, United States
  • Yusaku Matsuda
    RIBOMIC, Inc., Tokyo, Japan
  • Yosuke Nonaka
    RIBOMIC, Inc., Tokyo, Japan
  • Satoshi Futakawa
    RIBOMIC, Inc., Tokyo, Japan
  • Kazumasa Akita
    RIBOMIC, Inc., Tokyo, Japan
  • Toshiaki Nishihata
    RIBOMIC, Inc., Tokyo, Japan
  • Masatoshi Fujiwara
    RIBOMIC, Inc., Tokyo, Japan
  • Yusuf Ali
    RIBOMIC, Inc., Tokyo, Japan
  • Yoshikazu Nakamura
    RIBOMIC, Inc., Tokyo, Japan
    Institute of Medical Science, University of Tokyo, Tokyo, Japan
  • Footnotes
    Commercial Relationships   Robert Bhisitkul, AntriaBio/Rezolute (C), Apellis (F), Merck (R), Quark Pharmaceuticals (R), RIBOMIC, USA (C), Roche/Genentech (F), Zordera, Inc. (I); Yusaku Matsuda, RIBOMIC, Inc. (E); Yosuke Nonaka, RIBOMIC, Inc. (E); Satoshi Futakawa, RIBOMIC, Inc. (E); Kazumasa Akita, RIBOMIC, Inc. (E); Toshiaki Nishihata, RIBOMIC, Inc. (E); Masatoshi Fujiwara, RIBOMIC, Inc. (E); Yusuf Ali, RIBOMIC, Inc. (E); Yoshikazu Nakamura, RIBOMIC, Inc. (E)
  • Footnotes
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Investigative Ophthalmology & Visual Science July 2019, Vol.60, 976. doi:
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      Robert B Bhisitkul, Yusaku Matsuda, Yosuke Nonaka, Satoshi Futakawa, Kazumasa Akita, Toshiaki Nishihata, Masatoshi Fujiwara, Yusuf Ali, Yoshikazu Nakamura; Anti-angiogenic and anti-scarring dual action of an anti-Fibroblast Growth Factor-2 aptamer in animal models of retinal disease. Invest. Ophthalmol. Vis. Sci. 2019;60(9):976.

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

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Purpose : While fibroblast growth factor 2 (FGF2) initiates angiogenesis and scar formation in many tissue systems, its role in retinal diseases has not been defined. In animal models of choroidal neovascularization (CNV), we evaluated the pathogenic activity of FGF2, and the effects of a novel anti-FGF2 aptamer, RBM-007, in suppressing both angiogenesis and subretinal fibrosis.

Methods : In female C57BL/6J mice, Matrigel plugs mixed with 1 µg FGF2 were implanted subcutaneously in the right flank and daily intraperitoneal doses of RBM-007 were given. At day 7 explanted plugs were assessed for vessel growth by light microscopy. Laser-induced CNV was performed in both a mouse model and a rat model (male BN rats) using 532 nm and 50 µm spot size, immediately followed by intravitreal injections with: ranibizumab, RBM-007, or combination ranibizumab + RBM-007. CNV growth was quantified by FITC-dextran infusion and preparation of choroidal flat mounts for confocal microscopy. Subretinal fibrosis was assessed histologically in paraffin-embedded whole eye sections.

Results : In the mouse Matrigel plug assay, FGF2 stimulated robust new vessel growth; compared to saline vehicle, daily intraperitoneal injections of 1, 3, and 10 mg/kg produced reductions in blood vessel grades of 85, 88, and 96% respectively. In the mouse laser CNV model, at 7 days the combination of ranibizumab 10 μg/eye + RBM-007 6 μg/eye showed significant reduction in CNV area (controls mean 115426 ± 7253 (SE) pixels vs. 97478 ± 6651, p < 0.05, Dunnett’s test). In the rat CNV model, at 14 days compared to saline vehicle (mean 104534 ± 3478 pixels) significant reductions in CNV area (p < 0.05) were with found with intravitreal injection of ranibizumab 10 μg/eye (94849 ± 2159), and RBM-007 at doses of 5 to 45 μg/eye (92641 ± 2569 to 93586 ± 1964). Subretinal fibrosis formation at 6 weeks was graded and compared to saline vehicle (66.5% of spots grade 2 to 4 severity); eyes injected bi-weekly with RBM-007 15 μg/eye showed statistically significant reductions (p < 0.05) in severity of fibrosis with 2 injections (40.4%) and with 3 injections (40.6%).

Conclusions : Blockade of FGF2 with intravitreal injection of the aptamer RBM-007 led to suppression of both choroidal neovascularization and subretinal fibrosis in animal models. The dual action of RBM-007 suggests a novel pathway for treatment of neovascular AMD.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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