| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Lyzogubov, Valeriy Wu, Xiaobo Jha, Purushottam Tytarenko, Ruslana Triebwasser, Michael Kolar, Grant Bertram, Paula Bora, Puran S. Atkinson, John P. Bora, Nalini S. |
| Description |
Author Affiliation: Lyzogubov V ( Department of Ophthalmology, Pat and Willard Walker Eye Research Center, Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.); Wu X ( Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.); Jha P ( Department of Ophthalmology, Pat and Willard Walker Eye Research Center, Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.); Tytarenko R ( Department of Ophthalmology, Pat and Willard Walker Eye Research Center, Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.); Triebwasser M ( Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.); Kolar G ( Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri); Bertram P ( Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.); Bora PS ( Department of Ophthalmology, Pat and Willard Walker Eye Research Center, Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas.); Atkinson JP ( Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.); Bora NS ( 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.) |
| 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. |
| File Format |
HTM / HTML |
| ISSN |
00029440 |
| e-ISSN |
15252191 |
| DOI |
10.1016/j.ajpath.2014.06.001 |
| Journal |
The American Journal of Pathology |
| Issue Number |
9 |
| Volume Number |
184 |
| Language |
English |
| Publisher |
Elsevier (on behalf of the American Society for Investigative Pathology) |
| Publisher Date |
2014-09-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Choroidal Neovascularization Immunohistochemistry Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Mice, Inbred C57bl Antigens, Cd46 Discipline Pathology Metabolism Reverse Transcriptase Polymerase Chain Reaction Blotting, Western Enzyme-linked Immunosorbent Assay Mice, Knockout Animals Mice |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Pathology and Forensic Medicine |
