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Antiangiogenic effect of ALS‐L1023 on experimental choroidal neovascularization in mice
Author(s) -
KANG S,
RHO YJ
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.f057.x
Subject(s) - choroidal neovascularization , medicine , fluorescein angiography , neovascularization , umbilical vein , immunofluorescence , ophthalmology , pathology , mapk/erk pathway , andrology , kinase , angiogenesis , macular degeneration , chemistry , cancer research , retinal , immunology , biochemistry , antibody , in vitro
Purpose This study was conducted to evaluate the effect of ALS‐L1023 on experimental choroidal neovascularization (CNV) in mice. Methods C57BL/6 mice were administered either vehicle or ALS‐L1023 daily by oral gavage for three weeks (day 0‐21). CNV was induced in each mouse by rupturing Bruch’s membrane using laser photocoagulation (day 7). Two weeks after laser injury (day 21), the CNV lesions were evaluated by choroidal flat mounts using fluorescein‐labeled dextran, immunofluorescence staining with isolectin IB4, and fluorescence angiography. The effects of ALS‐L1023 on endothelial cell tube formation and on the expression of phosphorylated extracellular signal‐regulated kinase (p‐ERK1/2) were evaluated using human umbilical vein endothelial cells (HUVECs). Results ALS‐L1023 reduced the extent of CNV. The groups treated with 100 and 200 mg/kg/day showed 43.3 and 68.1 % reduction of CNV lesions, respectively, compared to the vehicle group (P < 0.001). The size of isolectin IB4 labeled area was also significantly decreased in the ALS‐L1023‐treated group (P < 0.001). On fluorescein angiography, ALS‐L1023‐treated mice had significantly less fluorescence leakage than vehicle‐treated mice. ALS‐L1023 decreased VEGF‐stimulated tube formation of HUVECs in a dose‐dependent manner. The expression of p‐ERK was suppressed by ALS‐L1023. Conclusion ALS‐L1023 can inhibit laser‐induced CNV in mice and may have therapeutic potential for treatment of choroidal neovascularization diseases.