%0 Journal Article
%T Infiltration of Proinflammatory M1 Macrophages into the Outer Retina Precedes Damage in a Mouse Model of Age-Related Macular Degeneration
%A Fernando Cruz-Guilloty
%A Ali M. Saeed
%A Jose J. Echegaray
%A Stephanie Duffort
%A Asha Ballmick
%A Yaohong Tan
%A Michel Betancourt
%A Eduardo Viteri
%A Ghansham C. Ramkhellawan
%A Eric Ewald
%A William Feuer
%A DeQiang Huang
%A Rong Wen
%A Li Hong
%A Hua Wang
%A James M. Laird
%A Abdoulaye Sene
%A Rajendra S. Apte
%A Robert G. Salomon
%A Joe G. Hollyfield
%A Victor L. Perez
%J International Journal of Inflammation
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/503725
%X 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. 1. Introduction Age-related macular degeneration (AMD) is the most common cause of legal blindness in the elderly population of developed countries with over 300,000 newly diagnosed patients per year in Europe and North America [1, 2]. It is widely believed that AMD starts with the insidious, slowly progressing ˇ°dryˇ± form (dry AMD) and can later develop into the more severe ˇ°wetˇ± AMD, which advances very rapidly and is characterized by abnormal development of blood vessels, a process called choroidal neovascularization (CNV) [3, 4] that affects the macular region of the retina and leads to loss of central vision. In turn, dry AMD without CNV can proceed to focal loss of the retinal pigment epithelium (RPE), termed geographic atrophy (GA), which is accompanied by loss of vision over these slowly expanding areas of RPE atrophy [5]. RPE loss or dysfunction renders the surrounding tissue vulnerable to damage by reactive oxygen species and loss of photoreceptor density ensues [6]. It has been recognized that accumulation of debris below the RPE in the macula, also known as drusen, is a risk factor for AMD. Identification of complement factor
%U http://www.hindawi.com/journals/iji/2013/503725/