Complement Regulatory Protein CD46 Protects against Choroidal Neovascularization in Mice
Open accessAbstract
Dysregulation of the complement system is increasingly recognized as a contributing factor in age-related macular degeneration. Although the complement regulator CD46 is expressed ubiquitously in humans, in mouse it was previously thought to be expressed only on spermatozoa. We detected CD46 mRNA and protein in the posterior ocular segment (neuronal retina, retinal pigment epithelium, and choroid) of wild-type (WT) C57BL/6J mice. Cd46(-/-) knockout mice exhibited increased levels of the membrane attack complex and of vascular endothelial growth factor (VEGF) in the retina and choroid. The Cd46(-/-) mice were also more susceptible to laser-induced choroidal neovascularization (CNV). In Cd46(-/-) mice, 19% of laser spots were positive for CNV at day 2 after treatment, but no positive spots were detected in WT mice. At day 3, 42% of laser spots were positive in Cd46(-/-) mice, but only 11% in WT mice. A fully developed CNV complex was noted in both Cd46(-/-) and WT mice at day 7; however, lesion size was significantly (P < 0.05) increased in Cd46(-/-) mice. Our findings provide evidence for expression of CD46 in the mouse eye and a role for CD46 in protection against laser-induced CNV. We propose that the Cd46(-/-) mouse has a greater susceptibility to experimental CNV because of insufficient complement inhibition, which leads to increased membrane attack complex deposition and VEGF expression.
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Inhibition of CD46 by gene knockout in mouse models led to increased VEGF production in the retina and choroid, increased MAC deposition on these tissues, increased susceptibility to laser-induced CNV, and degenerative changes in retinal tissues resembling an AMD phenotype.
“In addition, the inhibition of CD46 by gene knockout in mouse models led to increased VEGF production in the retina and choroid, increased MAC deposition on these tissues, increased susceptibility to laser-induced CNV, and degenerative changes in retinal tissues resembling an AMD phenotype [166,167].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [166]
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- Authors
- Lyzogubov, V., Wu, X., Jha, P., Tytarenko, R., Triebwasser, M., Kolar, G., Bertram, P., Bora, P. S., Atkinson, J. P., & Bora, N. S.
- Affiliations
- University of Arkansas for Medical Sciences (US)
- Washington University in St. Louis (US)
- University of Arkansas Medical Center (US)
- Corresponding author
- Bora, Nalini S.
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 184
- Issue
- 9
- Pages
- 2537-2548
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC4188132
- OpenAlex
- W2058278883
- Cited by
- 41
- References
- 52
- Citations by year
- 2025: 2 · 2024: 5 · 2023: 8 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 5 · 2016: 7 · 2015: 1
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Edward N. and Della L. Thome Memorial Foundation
- National Institutes of Health (DK-052574, RR016460)
- National Institute of General Medical Sciences (R01GM099111)
- National Institute of Allergy and Infectious Diseases (R01AI041592)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK052574)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR048335)
- National Center for Research Resources (P20RR016460)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- CD46, complement regulatory proteins, choroidal neovascularization, age-related macular degeneration, complement inhibition, membrane attack complex, vascular endothelial growth factor, laser-induced choroidal neovascularization, retinal pigment epithelium, choroid
- MeSH terms
- Animals, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Mice, Inbred C57BL, Blotting, Western, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Choroidal Neovascularization, Mice, Membrane Cofactor Protein
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