Cd59, a Complement Regulatory Protein, Controls Choroidal Neovascularization in a Mouse Model of Wet-type Age-related Macular Degeneration.
From: Department of Ophthalmology, Jones Eye Institute, Pat and Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. NBora@UAMS.edu
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Feb 2007
- ISSN: 0022-1767
- Volume: 178
- Issue: 3
- Pages: 1783-90
- Medium: Print
- Language: English
- Citation (JAMA): Bora Nalini S, Kaliappan Sankaranarayanan, Jha Purushottam, et al. Cd59, a Complement Regulatory Protein, Controls Choroidal Neovascularization in a Mouse Model of Wet-type Age-related Macular Degeneration.. J. Immunol. Feb 2007;178:1783-90
Abstract
We have shown that membrane attack complex (MAC) formation via the activation of the alternative pathway plays a central role in the laser-induced choroidal neovascularization (CNV). This study was undertaken to understand the role of a complement regulatory protein, CD59, which controls MAC assembly and function, in this model. CNV was induced by laser photocoagulation in C57BL/6 and Cd59a(-/-) mice using an argon laser. Animals from each group were sacrificed on day 1, 3, 5, and 7 postlaser. Retinal pigment epithelium-choroid-scleral tissue was examined to determine the incidence and size of CNV complex, and semiquantitative RT-PCR and Western blot analysis for CD59a was studied. Recombinant soluble mouse CD59a-IgG2a fusion (rsCD59a-Fc) protein was injected via i.p. or intravitreal routes 24 h before laser. Our results demonstrated that CD59a (both mRNA and protein) was down-regulated during laser-induced CNV. Cd59a(-/-) mice developed CNV complex early in the disease process. Increased MAC deposition was also observed in these Cd59a(-/-) mice. Administration of rsCD59a-Fc inhibited the development of CNV complex in the mouse model by blocking MAC formation and also inhibited expression of angiogenic growth factors. These data provide strong evidence that CD59a plays a crucial role in regulating complement activation and MAC formation essential for the release of growth factors that drive the development of laser-induced CNV in mice. Thus, our results suggest that the inhibition of complement by soluble CD59 may provide a novel therapeutic alternative to current treatment.
Mesh Headings (Keywords): Animals, Antigens, CD59, Choroidal Neovascularization, Complement Activation, Complement Membrane Attack Complex, Disease Models, Animal, Down-Regulation, Immunoglobulin G, Intercellular Signaling Peptides and Proteins, Lasers, Macular Degeneration, Mice, Mice, Knockout, Recombinant Fusion Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 17237428
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