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Deze abstract is toegekend aan sessie FRO: Fund for Research in Ophthalmology
TitelFRO: The effect of AMA0428, a novel rock inhibitor, in a model of wet age-related macular degeneration
Abstract Nr.1029
DoelRho kinase (ROCK) is associated with VEGF-driven angiogenesis and is involved in inflammation and fibrosis. Therefore, the effect of a novel ROCK inhibitor, AMA0428, was studied in wet age-related macular degeneration (AMD).
MethodesThe effect of AMA0428 on human brain microvascular endothelial cells (HBMEC), human brain vascular pericytes (HBVP) and human tenon fibroblasts (HTF) was determined by measuring cell viability (WST-1), apoptosis (caspase 3/7) and 2 migration assays (scratch and under-agarose) The in vivo response was investigated using a laser-induced choroidal neovascularization (CNV) mouse model. Intravitreal injections were given on day 0, 4, 10 and 20 with AMA0428, murine anti-VEGFR Ab (DC101) or placebo. Outcome was assessed by analysis of inflammation (CD45), angiogenesis (FITC-dextran), vessel leakage (Texas Red-conjugated Dextran and FITC-labeled lectin) and fibrosis (Collagen I).
ResultatenAMA0428 dose-dependently reduced proliferation and VEGF-induced migration of HBMEC and HTF. No significant effect was seen on HBVP proliferation; however, migration and pericyte recruitment were increased. There was no apoptosis induction. AMA0428 significantly reduced CNV and vessel leakage 2 weeks after laser treatment, comparable to DC101. In addition, AMA0428 inhibited inflammation on day 5 by 20% and collagen deposition on day 30 by 39% while DC101 had no effect on inflammation nor fibrosis.
ConclusieOur data suggest that targeting ROCK with AMA0428 not only reduces neoangiogenesis, but also blocks inflammation and fibrosis (contrary to anti-VEGF). These results point to a potential therapeutic benefit of ROCK inhibition in wet AMD.
Auteur 1
NaamHOLLANDERS
InitialenK
InstituutKUL
StadLeuven
Auteur 2
NaamVan Bergen
InitialenT
InstituutKUL
StadLeuven
Auteur 3
NaamVandewalle
InitialenE
InstituutKUL
StadLeuven
Auteur 4
NaamCastermans
InitialenK
InstituutAmakem
StadDiepenbeek
Auteur 5
NaamKindt
InitialenN
InstituutAmakem
StadDiepenbeek
Auteur 6
NaamMoons
InitialenL
InstituutKUL
StadLeuven
Auteur 7
NaamStalmans
InitialenI
InstituutKUL
StadLeuven
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