title: Complement regulatory protein CD46 protects against choroidal neovascularization in mice.
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.
authors.affiliation: Department of Ophthalmology, Pat and Willard Walker Eye Research Center, Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Valeriy
authors.initials: V
authors.lastname: Lyzogubov
authors.affiliation: Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Pat and Willard Walker Eye Research Center, Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Purushottam
authors.initials: P
authors.lastname: Jha
authors.affiliation: Department of Ophthalmology, Pat and Willard Walker Eye Research Center, Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Ruslana
authors.initials: R
authors.lastname: Tytarenko
authors.affiliation: Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Michael
authors.initials: M
authors.lastname: Triebwasser
authors.affiliation: Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Grant
authors.initials: G
authors.lastname: Kolar
authors.affiliation: Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Paula
authors.initials: P
authors.lastname: Bertram
authors.affiliation: Department of Ophthalmology, Pat and Willard Walker Eye Research Center, Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Puran S
authors.initials: PS
authors.lastname: Bora
authors.affiliation: Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: John P
authors.initials: JP
authors.lastname: Atkinson
authors.affiliation: Department of Ophthalmology, Pat and Willard Walker Eye Research Center, Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas. Electronic address: nbora@uams.edu.
authors.forename: Nalini S
authors.initials: NS
authors.lastname: Bora
mesh_terms: D000818:Animals; D015153:Blotting, Western; D020256:Choroidal Neovascularization / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D051916:Membrane Cofactor Protein / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein