Infiltration of proinflammatory m1 macrophages into the outer retina precedes damage in a mouse model of age-related macular degeneration

Fernando Cruz-Guilloty, Ali M. Saeed, Jose J. Echegaray, Stephanie Duffort, Asha Ballmick, Yaohong Tan, Michel Betancourt, Eduardo Viteri, Ghansham C. Ramkhellawan, Eric Ewald, William Feuer, Deqiang Huang, Rong Wen, Li Hong, Hua Wang, James M. Laird, Abdoulaye Sene, Rajendra S. Apte, Robert G. Salomon, Joe G. HollyfieldVictor L. Perez

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


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.

Original languageEnglish
Article number503725
JournalInternational Journal of Inflammation
StatePublished - 2013


Dive into the research topics of 'Infiltration of proinflammatory m1 macrophages into the outer retina precedes damage in a mouse model of age-related macular degeneration'. Together they form a unique fingerprint.

Cite this