Abstract

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. © 2014 American Society for Investigative Pathology.

Department(s)

Biological Sciences

Publication Status

Open Access

Comments

National Institutes of Health, Grant P20-RR016460

International Standard Serial Number (ISSN)

1525-2191; 0002-9440

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2025 Elsevier, All rights reserved.

Publication Date

01 Jan 2014

PubMed ID

25019227

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