Intravitreal inhibition of complement C5a reduces choroidal neovascularization in mice.
Graefes Arch Clin Exp Ophthalmol
; 253(10): 1695-704, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-25981118
ABSTRACT
PURPOSE:
To investigate the influence of complement component C5a inhibition on laser-induced choroidal neovascularization (CNV) in mice using a C5a specific L-aptamer.METHODS:
In C57BL/6 J mice CNV was induced by argon-laser, C5a-inhibitor (NOX-D20) was intravitreally injected in three concentrations 0.3, 3.0, and 30 mg/ml. The unPEGylated derivate (NOX-D20001) was applied at 3.0 mg/ml; the vehicle (5 % glucose) was injected in controls. Vascular leakage was evaluated using fluorescence angiography, CNV area was examined immunohistochemically. Activated immune cells surrounding the CNV lesion and potential cytotoxicity were analyzed.RESULTS:
Compared to controls, CNV areas were significantly reduced after NOX-D20 injection at a concentration of 0.3 and 3.0 mg/ml (p = 0.042; p = 0.016). NOX-D20001 significantly decreased CNV leakage but not the area (p = 0.007; p = 0.276). At a concentration of 30 mg/ml, NOX-D20 did not reveal significant effects on vascular leakage or CNV area (p = 0.624; p = 0.121). The amount of CD11b positive cells was significantly reduced after treatment with 0.3 and 3.0 mg/ml NOX-D20 (p = 0.027; p = 0.002). No adverse glial cell proliferation or increased apoptosis were observed at effective dosages.CONCLUSIONS:
Our findings demonstrate that the targeted inhibition of complement component C5a reduces vascular leakage and neovascular area in laser-induced CNV in mice. NOX-D20 was proven to be an effective and safe agent that might be considered as a therapeutic candidate for CNV treatment. The deficiency of activated immune cells highlights promising new aspects in the pathology of choroidal neovascularization, and warrants further investigations.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Serina Endopeptidases
/
Complemento C5a
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Neovascularização de Coroide
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Aptâmeros de Nucleotídeos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Graefes Arch Clin Exp Ophthalmol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Alemanha