Local acting Sticky-trap inhibits vascular endothelial growth factor dependent pathological angiogenesis in the eye

Iacovos P. Michael, Peter D. Westenskow, Sabiha Hacibekiroglu, Alissa Cohen Greenwald, Brian G. Ballios, Toshihide Kurihara, Zhijie Li, Carmen M. Warren, Puzheng Zhang, Edith Aguilar, Laura Donaldson, Valentina Marchetti, Takeshi Baba, Samer M. Hussein, Hoon Ki Sung, M. Luisa Iruela-Arispe, James M. Rini, Derek Van der Kooy, Martin Friedlander, Andras Nagy

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9 Citations (Scopus)

Abstract

Current therapeutic antiangiogenic biologics used for the treatment of pathological ocular angiogenesis could have serious side effects due to their interference with normal blood vessel physiology. Here, we report the generation of novel antivascular endothelial growth factor-A (VEGF) biologics, termed VEGF "Sticky-traps," with unique properties that allow for local inhibition of angiogenesis without detectable systemic side effects. Using genetic and pharmacological approaches, we demonstrated that Sticky-traps could locally inhibit angiogenesis to at least the same extent as the original VEGF-trap that also gains whole-body access. Sticky-traps did not cause systemic effects, as shown by uncompromised wound healing and normal tracheal vessel density. Moreover, if injected intravitreally, recombinant Sticky-trap remained localized to various regions of the eye, such as the inner-limiting membrane and ciliary body, for prolonged time periods, without gaining access either to the photoreceptors/choriocapillaris area or the circulation. These unique pharmacological characteristics of Sticky-trap could allow for safe treatment of pathological angiogenesis in patients with diabetic retinopathy and retinopathy of pre-maturity.

Original languageEnglish
Pages (from-to)604-623
Number of pages20
JournalEMBO Molecular Medicine
Volume6
Issue number5
DOIs
Publication statusPublished - 2014 May

Keywords

  • Angiogenesis
  • Diabetic retinopathy
  • Retinopathy of prematurity
  • Sticky-trap
  • VEGF

ASJC Scopus subject areas

  • Molecular Medicine

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  • Cite this

    Michael, I. P., Westenskow, P. D., Hacibekiroglu, S., Greenwald, A. C., Ballios, B. G., Kurihara, T., Li, Z., Warren, C. M., Zhang, P., Aguilar, E., Donaldson, L., Marchetti, V., Baba, T., Hussein, S. M., Sung, H. K., Iruela-Arispe, M. L., Rini, J. M., Van der Kooy, D., Friedlander, M., & Nagy, A. (2014). Local acting Sticky-trap inhibits vascular endothelial growth factor dependent pathological angiogenesis in the eye. EMBO Molecular Medicine, 6(5), 604-623. https://doi.org/10.1002/emmm.201303708