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Cet abstract a été assigné à session FRO: Fund for Research in Ophthalmology
TitreFRO: The effect of AMA0428, a novel rock inhibitor, in a model of wet age-related macular degeneration
Abstract Nr.1029
ButRho 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).
MéthodesThe 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).
RésultatsAMA0428 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.
ConclusionOur 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
NomHOLLANDERS
InitialesK
InstitutKUL
VilleLeuven
Auteur 2
NomVan Bergen
InitialesT
InstitutKUL
VilleLeuven
Auteur 3
NomVandewalle
InitialesE
InstitutKUL
VilleLeuven
Auteur 4
NomCastermans
InitialesK
InstitutAmakem
VilleDiepenbeek
Auteur 5
NomKindt
InitialesN
InstitutAmakem
VilleDiepenbeek
Auteur 6
NomMoons
InitialesL
InstitutKUL
VilleLeuven
Auteur 7
NomStalmans
InitialesI
InstitutKUL
VilleLeuven
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