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

• DOI: 10.1155/2013/503725
• Publication Date: 2013-03-07T21:28:19Z
• Authors: Fernando Cruz-Gui...; Ali M. Saeed; Jose J. Echegaray; Stephanie Duffort; Asha Ballmick; Yaohong Tan; Michel Betancourt; Eduardo Viteri; Ghansham C. Ramkh...; 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. Hollyfield; Victor L. Perez
• Keywords: Proinflammatory cytokine; Infiltration (HVAC)

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