We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
T Cells and Macrophages Responding to Oxidative Damage Cooperate in Pathogenesis of a Mouse Model of Age-Related Macular Degeneration.
- Authors
Cruz-Guilloty, Fernando; Saeed, Ali M.; Duffort, Stephanie; Cano, Marisol; Ebrahimi, Katayoon B.; Ballmick, Asha; Tan, Yaohong; Wang, Hua; Laird, James M.; Salomon, Robert G.; Handa, James T.; Perez, Victor L.
- Abstract
Age-related macular degeneration (AMD) is a major disease affecting central vision, but the pathogenic mechanisms are not fully understood. Using a mouse model, we examined the relationship of two factors implicated in AMD development: oxidative stress and the immune system. Carboxyethylpyrrole (CEP) is a lipid peroxidation product associated with AMD in humans and AMD-like pathology in mice. Previously, we demonstrated that CEP immunization leads to retinal infiltration of pro-inflammatory M1 macrophages before overt retinal degeneration. Here, we provide direct and indirect mechanisms for the effect of CEP on macrophages, and show for the first time that antigen-specific T cells play a leading role in AMD pathogenesis. In vitro, CEP directly induced M1 macrophage polarization and production of M1-related factors by retinal pigment epithelial (RPE) cells. In vivo, CEP eye injections in mice induced acute pro-inflammatory gene expression in the retina and human AMD eyes showed distinctively diffuse CEP immunolabeling within RPE cells. Importantly, interferon-gamma (IFN-γ) and interleukin-17 (IL-17)-producing CEP-specific T cells were identified ex vivo after CEP immunization and promoted M1 polarization in co-culture experiments. Finally, T cell immunosuppressive therapy inhibited CEP-mediated pathology. These data indicate that T cells and M1 macrophages activated by oxidative damage cooperate in AMD pathogenesis.
- Subjects
T cells; MACROPHAGES; OXIDATIVE stress; LABORATORY mice; AGE factors in retinal degeneration; PYRROLES; INTERFERON gamma release tests
- Publication
PLoS ONE, 2014, Vol 9, Issue 2, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0088201