Journal
INTERNATIONAL JOURNAL OF INFLAMMATION
Volume 2013, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2013/503725
Keywords
-
Categories
Funding
- Edward N. & Della L. Thome Memorial Foundation
- Bank of America N. A. Trustee Award Program in Macular Degeneration Research
- NIH [P30EY14801, R01-GM21249, R01EY018586, R01-EY019287, R01-EY014240]
- NIH Vision Core Grant [P30EY02687]
- Carl Marshall Reeves and Mildred Almen Reeves Foundation Award
- International Retina Research Foundation
- American Health Assistance Foundation
- Thome Foundation
- Research to Prevent Blindness (Unrestricted Grant to Washington University)
- Macular Vision Research Foundation
- Foundation Fighting Blindness
- Llura and Gordon Gund Foundation
- Sheila and David Fuente Graduate Programin Cancer Biology, Sylvester Comprehensive Cancer Center
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available