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International Journal of Inflammation
Volume 2013 (2013), Article ID 503725, 12 pages
Research Article

Infiltration of Proinflammatory M1 Macrophages into the Outer Retina Precedes Damage in a Mouse Model of Age-Related Macular Degeneration

1Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA
2Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
3Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA
4Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA
5Department of Ophthalmology, Cole Eye Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, OH 44195, USA
6Ophthalmology, Immunology & Microbiology, University of Miami Miller School of Medicine, Bascom Palmer Eye Institute, Miami, FL 33136, USA

Received 17 October 2012; Revised 20 December 2012; Accepted 24 January 2013

Academic Editor: Robert B. Nussenblatt

Copyright © 2013 Fernando Cruz-Guilloty et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Age-related macular degeneration (AMD) is a major cause of blindness in the developed world. Oxidative stress and inflammation are implicated in AMD, but precise mechanisms remain poorly defined. Carboxyethylpyrrole (CEP) is an AMD-associated lipid peroxidation product. We previously demonstrated that mice immunized with CEP-modified albumin developed AMD-like degenerative changes in the outer retina. Here, we examined the kinetics of lesion development in immunized mice and the presence of macrophages within the interphotoreceptor matrix (IPM), between the retinal pigment epithelium and photoreceptor outer segments. We observed a significant and time-dependent increase in the number of macrophages in immunized mice relative to young age-matched controls prior to overt pathology. These changes were more pronounced in BALB/c mice than in C57BL/6 mice. Importantly, IPM-infiltrating macrophages were polarized toward the M1 phenotype but only in immunized mice. Moreover, when Ccr2-deficient mice were immunized, macrophages were not present in the IPM and no retinal lesions were observed, suggesting a deleterious role for these cells in our model. This work provides mechanistic evidence linking immune responses against oxidative damage with the presence of proinflammatory macrophages at sites of future AMD and experimentally demonstrates that manipulating immunity may be a target for modulating the development of AMD.