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Rho‐associated kinase inhibition prevents pathological neovascularization after corneal trauma
Author(s) -
SIJNAVE D,
VAN BERGEN T,
VANDEWALLE E,
STALMANS I
Publication year - 2014
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2014.4424.x
Subject(s) - corneal neovascularization , in vivo , cd31 , neovascularization , angiogenesis , endothelial stem cell , in vitro , cornea , medicine , vascular endothelial growth factor , corneal inflammation , cell growth , inflammation , andrology , chemistry , pathology , ophthalmology , cancer research , immunology , biology , vegf receptors , biochemistry , microbiology and biotechnology
Purpose The aim of this study was to investigate the effect of AMA0526, a selective and locally acting ROCK inhibitor on endothelial cells in vitro and in vivo by using a mouse corneal neovascularization (NV) model. Methods In vitro, the effect of AMA0526 (0.1; 1 and 10 µM) on endothelial cell proliferation and FBS‐stimulated migration was investigated. A mouse corneal micropocket (MCM) model was used to study the in vivo effect of the ROCK inhibitor on corneal NV. A bFGF pellet was implanted in both eyes and topical administration was applied once daily using AMA0526 (0.1%) in one eye and vehicle (PEG/H2O) in the contralateral eye. Outcome was investigated by analysing vessel length, clock hours and NV area 7 days post implantation. Histological outcome was evaluated by immunohistochemical staining for inflammation (CD45) and angiogenesis (CD31). Results HBMEC and HUVEC proliferation was significantly inhibited in a dose‐dependent manner by ROCK inhibition. AMA0526 (1 and 10 µM) also induced significant reduction of FBS‐stimulated endothelial cell migration, respectively by 29% and 40%. In the MCM model, AMA0526 treatment significantly reduced NV area by 28% and vessel length by 28%, as compared to vehicle treated. These effects were associated with a decreased infiltration of inflammatory cells (P<0.05; 32% reduction) and a reduced blood vessel density (P<0.05; 40% reduction) at day 7. Conclusion AMA0526 inhibits endothelial cell proliferation and migration in vitro and is efficacious in reducing corneal NV after bFGF micropocket implantation. These results indicate that ROCK inhibition by AMA0526 may have therapeutic value for the treatment of pathological corneal NV.