TY - JOUR
T1 - Complement activation via alternative pathway is critical in the development of laser-induced choroidal neovascularization
T2 - role of factor B and factor H
AU - Bora, Nalini S.
AU - Kaliappan, Sankaranarayanan
AU - Jha, Purushottam
AU - Xu, Qin
AU - Sohn, Jeong Hyeon
AU - Dhaulakhandi, Dhara B.
AU - Kaplan, Henry J.
AU - Bora, Puran S.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2006/8/1
Y1 - 2006/8/1
N2 - The objective of this study was to explore the role of classical, lectin, and alternative pathways of complement activation in laser-induced choroidal neovascularization (CNV). The classical and alternative pathways were blocked in C57BL/6 mice by small interfering RNAs (siRNA) directed against C1q and factor B, respectively. C4-/- mice developed CNV similar to their wild-type controls and inhibition of CIq by siRNA had no effect on the development of CNV. In contrast, CNV was significantly inhibited (p < 0.001) in C5-/- mice and C57BL/6 mice treated with factor B siRNA. Inhibition of the alternative pathway by factor B siRNA resulted in decreased levels of membrane attack complex and angiogenic factors-vascular endothelial growth factor and TGF-β2. Furthermore, factor B was up-regulated in complement sufficient C57BL/6 mice at day 1 postlaser and remained elevated at day 7. Significantly reduced levels of factor H were observed at day 3 in these animals. In conclusion, our results demonstrate that activation of the factor B-dependent alternative pathway, but not the classical or lectin pathways, was essential for the development of CNV in mouse model of laser-induced CNV. Thus, specific blockade of the alternative pathway may represent a therapeutically relevant strategy for the inhibition of CNV.
AB - The objective of this study was to explore the role of classical, lectin, and alternative pathways of complement activation in laser-induced choroidal neovascularization (CNV). The classical and alternative pathways were blocked in C57BL/6 mice by small interfering RNAs (siRNA) directed against C1q and factor B, respectively. C4-/- mice developed CNV similar to their wild-type controls and inhibition of CIq by siRNA had no effect on the development of CNV. In contrast, CNV was significantly inhibited (p < 0.001) in C5-/- mice and C57BL/6 mice treated with factor B siRNA. Inhibition of the alternative pathway by factor B siRNA resulted in decreased levels of membrane attack complex and angiogenic factors-vascular endothelial growth factor and TGF-β2. Furthermore, factor B was up-regulated in complement sufficient C57BL/6 mice at day 1 postlaser and remained elevated at day 7. Significantly reduced levels of factor H were observed at day 3 in these animals. In conclusion, our results demonstrate that activation of the factor B-dependent alternative pathway, but not the classical or lectin pathways, was essential for the development of CNV in mouse model of laser-induced CNV. Thus, specific blockade of the alternative pathway may represent a therapeutically relevant strategy for the inhibition of CNV.
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U2 - 10.4049/jimmunol.177.3.1872
DO - 10.4049/jimmunol.177.3.1872
M3 - Article
C2 - 16849499
AN - SCOPUS:33746190776
SN - 0022-1767
VL - 177
SP - 1872
EP - 1878
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -