Complement activation via alternative pathway is critical in the development of laser-induced choroidal neovascularization: role of factor B and factor H

Nalini S. Bora, Sankaranarayanan Kaliappan, Purushottam Jha, Qin Xu, Jeong Hyeon Sohn, Dhara B. Dhaulakhandi, Henry J. Kaplan, Puran S. Bora

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1872-1878
Number of pages7
JournalJournal of Immunology
Volume177
Issue number3
DOIs
StatePublished - Aug 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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