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

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

doi:10.4049/jimmunol.177.3.1872

Cited by 125Complement system in diseasesRetinal Diseases and TreatmentsOcular Diseases and Behçet’s Syndrome

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

Bora, Nalini S, Kaliappan, Sankaranarayanan, Jha, Purushottam, Xu, Qin, Sohn, Jeong-Hyeon, Dhaulakhandi, Dhara B, Kaplan, Henry J, Bora, Puran S·2006·The Journal of Immunology

DOI 10.4049/jimmunol.177.3.1872

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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 C1q 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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Several experiments using mouse models of laser-induced CNV have demonstrated that all complement pathways, particularly the alternative and terminal pathways, play a significant role in angiogenesis.
“Several experiments using mouse models of laser-induced CNV have demonstrated that all complement pathways, particularly the alternative and terminal pathways, play a significant role in angiogenesis [150,152,153,154,155,156,157,158,159,160,161,162,163].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [154]

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Authors: Bora, N. S., Kaliappan, S., Jha, P., Xu, Q., Sohn, J.-H., Dhaulakhandi, D. B., Kaplan, H. J., & Bora, P. S.
Affiliations: University of Arkansas for Medical Sciences (US)
University of Louisville (US)
ORCID: Xu, Qin
Kaplan, Henry J
Bora, Puran S
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2006-08-01
Volume: 177
Issue: 3
Pages: 1872-1878
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.177.3.1872
OpenAlex: W1585939626
Cited by: 124
References: 37
Citations by year: 2025: 1 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 4 · 2020: 7 · 2019: 1 · 2018: 5 · 2017: 11 · 2016: 5 · 2015: 8 · 2014: 9 · 2013: 4 · 2012: 12
FWCI: 3.42
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Eye Institute (R01EY013335, R01EY014623, EY 014623, EY-13335)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
Keywords: choroidal neovascularization, laser-induced CNV, alternative complement pathway, factor B, complement factor H, complement activation, C1q, C5, membrane attack complex, angiogenesis, vascular endothelial growth factor, TGF-beta2, siRNA knockdown
MeSH terms: Animals, Complement Pathway, Alternative, Complement C4, Complement C5, Injections, Intravenous, Lasers, Male, Mice, Inbred C57BL, Complement Factor B, Down-Regulation, Up-Regulation, Complement C1q, Complement Membrane Attack Complex, Transforming Growth Factor beta, Complement Factor H, Mice, Knockout, Choroidal Neovascularization, RNA, Small Interfering, Vascular Endothelial Growth Factor A, Mice, Transforming Growth Factor beta2

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

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