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This abstract is assigned to session FRO: Fund for Research in Ophthalmology

Title	FRO: The effect of AMA0428, a novel rock inhibitor, in a model of wet age-related macular degeneration
Abstract Nr.	1029

Purpose	Rho 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).
Methods	The 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).
Results	AMA0428 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.
Conclusion	Our 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.

Authors 1

Last name	HOLLANDERS
Initials	K
Department	KUL
City	Leuven

Authors 2

Last name	Van Bergen
Initials	T
Department	KUL
City	Leuven

Authors 3

Last name	Vandewalle
Initials	E
Department	KUL
City	Leuven

Authors 4

Last name	Castermans
Initials	K
Department	Amakem
City	Diepenbeek

Authors 5

Last name	Kindt
Initials	N
Department	Amakem
City	Diepenbeek

Authors 6

Last name	Moons
Initials	L
Department	KUL
City	Leuven

Authors 7

Last name	Stalmans
Initials	I
Department	KUL
City	Leuven