Open AccessLocal acting S ticky‐trap inhibits vascular endothelial growth factor dependent pathological angiogenesis in the eye
Author(s) -
Michael Iacovos P,
Westenskow Peter D,
Hacibekiroglu Sabiha,
Greenwald Alissa Cohen,
Ballios Brian G,
Kurihara Toshihide,
Li Zhijie,
Warren Carmen M,
Zhang Puzheng,
Aguilar Edith,
Donaldson Laura,
Marchetti Valentina,
Baba Takeshi,
Hussein Samer M,
Sung HoonKi,
IruelaArispe M Luisa,
Rini James M,
Kooy Derek,
Friedlander Martin,
Nagy Andras
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201303708
Subject(s) - angiogenesis , vascular endothelial growth factor , diabetic retinopathy , neovascularization , cancer research , growth factor , medicine , blood vessel , pathological , vascular endothelial growth factor a , microbiology and biotechnology , biology , pathology , endocrinology , vegf receptors , diabetes mellitus , receptor
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.