Local acting S ticky‐trap inhibits vascular endothelial growth factor dependent pathological angiogenesis in the eye

Autor: Puzheng Zhang, Andras Nagy, Samer M.I. Hussein, Derek van der Kooy, Peter D. Westenskow, Hoon Ki Sung, Brian G. Ballios, Zhijie Li, Takeshi Baba, Martin Friedlander, Alissa Cohen Greenwald, Sabiha Hacibekiroglu, Edith Aguilar, M. Luisa Iruela-Arispe, Iacovos P. Michael, James M. Rini, Valentina Marchetti, Laura Donaldson, Toshihide Kurihara, Carmen M. Warren
Rok vydání: 2014
Předmět:
Zdroj: EMBO Molecular Medicine. 6:604-623
ISSN: 1757-4684
1757-4676
Popis: 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.
Databáze: OpenAIRE
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