TY - JOUR
T1 - Local acting Sticky-trap inhibits vascular endothelial growth factor dependent pathological angiogenesis in the eye
AU - Michael, Iacovos P.
AU - Westenskow, Peter D.
AU - Hacibekiroglu, Sabiha
AU - Greenwald, Alissa Cohen
AU - Ballios, Brian G.
AU - Kurihara, Toshihide
AU - Li, Zhijie
AU - Warren, Carmen M.
AU - Zhang, Puzheng
AU - Aguilar, Edith
AU - Donaldson, Laura
AU - Marchetti, Valentina
AU - Baba, Takeshi
AU - Hussein, Samer M.
AU - Sung, Hoon Ki
AU - Iruela-Arispe, M. Luisa
AU - Rini, James M.
AU - Van der Kooy, Derek
AU - Friedlander, Martin
AU - Nagy, Andras
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Diabetic retinopathy
KW - Retinopathy of prematurity
KW - Sticky-trap
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=84899868974&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899868974&partnerID=8YFLogxK
U2 - 10.1002/emmm.201303708
DO - 10.1002/emmm.201303708
M3 - Article
C2 - 24705878
AN - SCOPUS:84899868974
SN - 1757-4676
VL - 6
SP - 604
EP - 623
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
IS - 5
ER -